Cyclosporin a treatment is able to revert the decrease in circulating GH and IGF-I and the increase in IGFBPs induced by adjuvant arthritis.

The aim of this study was to find out whether cyclosporin A administration is able to revert the decrease in circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) and the increase in IGF-binding proteins (IGFBPs) levels caused by adjuvant-induced arthritis in rats. Male Sprague-Dawley rats were intradermically injected with Freund's adjuvant or vehicle. Fourteen days later, rats were randomly divided into two groups - one injected with cyclosporin (15 mg/kg) and the other with vehicle from day 16 to 23 after adjuvant injection. Arthritis decreased body weight gain and serum concentrations of GH. Cyclosporin administration to arthritic rats prevented both effects, whereas cyclosporin had no effect in control rats. Arthritis decreased serum concentrations of IGF-I (p < 0.01), but increased IGFBPs. Cyclosporin administration increased circulating IGF-I, and there was a negative correlation between circulating IGF-I and arthritis index scores in arthritic rats injected with cyclosporin (p < 0.05). Cyclosporin treatment did not alter serum IGFBPs levels in control rats, whereas cyclosporin administration normalised IGFBPs in arthritic rats. These results indicate that the effects of cyclosporin administration on the GH-IGF-IGFBPs system may partly mediate its beneficial effect on body weight in arthritic rats.     

Effect of vitamin E on adjuvant arthritis in rats

Adjuvant arthritis was induced in rats fed a diet deficient in or supplemented with vitamin E, and its severity was scored according to the macroscopic findings of their legs, tails, and ears. The average score so obtained was higher in the vitamin E-deficient diet group than in the group of rats supplemented with vitamin E. Whereas the A/G ratio remained depressed in vitamin E-deficient rats, rats on a vitamin E-supplemented diet showed a fast recovery from A/G-ratio depression. The serum levels of beta-glucuronidase and acid phosphatase were elevated after administration of an adjuvant. The serum levels of these lysosomal enzymes showed a remarkable increase in rats fed a vitamin E-deficient diet, while the elevation in lysosomal enzyme levels in rats fed a vitamin E-supplemented diet was inhibited. The levels of thiobarbituric acid (TBA) reactants in the synovia were elevated at 2 weeks after exposure to the adjuvant and were decreased thereafter. In rats maintained on a diet supplemented with vitamin E, on the other hand, the increase in synovial level of TBA reactive substances was inhibited. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation and that antioxidants, such as vitamin E, may be beneficial for arthritis.     

Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP-induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.     

Inhibitory effect of amygdalin on lipopolysaccharide-inducible TNF-alpha and IL-1beta mRNA expression and carrageenan-induced rat arthritis

Amygdalin is a cyanogenic glycoside plant compound found in the seeds of rosaceous stone fruits. We evaluated the antiinflammatory and analgesic activities of amygdalin, using an in vitro lipopolysaccharide (LPS)-induced cell line and a rat model with carrageenan-induced ankle arthritis. One mM amygdalin significantly inhibited the expression of TNF-alpha and IL-1beta mRNAs in LPS-treated RAW 264.7 cells. Amygdalin (0.005, 0.05, and 0.1 mg/kg) was intramuscularly injected immediately after the induction of carrageenan-induced arthritic pain in rats, and the anti-arthritic effect of amygdalin was assessed by measuring the weight distribution ratio of the bearing forces of both feet and the ankle circumference, and by analyzing the expression levels of three molecular markers of pain and inflammation (c-Fos, TNF-alpha, and IL-1beta) in the spinal cord. The hyperalgesia of the arthritic ankle was alleviated most significantly by the injection of 0.005 mg/kg amygdalin. At this dosage, the expressions of c-Fos, TNF-alpha, and IL-1beta in the spinal cord were significantly inhibited. However, at dosage greater than 0.005 mg/kg, the painrelieving effect of amygdalin was not observed. Thus, amygdalin treatment effectively alleviated responses to LPStreatment in RAW 264.7 cells and carrageenan-induced arthritis in rats, and may serve as an analgesic for relieving inflammatory pain.     

Effects of histamine and related compounds on thyrotropin secretion in rats

The effects of histamine (HA) and related compounds on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Histidine (1.0 g/kg), HA (5.0 mg/kg) or histamine antagonists mepyramine (MP) (100 mg/kg) or famotidine (FA) (5.0 mg/kg) were injected intraperitoneally, and the rats were decapitated at various intervals after the injection. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after histidine or HA injection, decreased significantly after FA injection, but was not changed by MP. The plasma ir-TRH concentration did not change significantly after injection of these drugs. The plasma TSH levels decreased significantly in a dose-related manner after histidine or HA injection and increased significantly in a dose-related manner after FA injection. The plasma thyroid hormone levels showed no changes. In the FA-pretreated group, the inhibitory effect of histidine or HA on TSH levels was prevented, but not in the MP-pretreated group. The plasma ir-TRH and TSH responses to cold were inhibited by histidine or HA and enhanced by FA. The plasma TSH response to TRH was inhibited by histidine or HA and enhanced by FA. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after histidine, HA, MP or FA was not different from that of the control. These findings suggest that histamine may act both on the hypothalamus and the pituitary to inhibit TRH and TSH release, and that its effects may be mediated via H2-receptor.     

Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration

We aimed to study the alterations in serum homocysteine levels and endothelium-dependent and -independent vascular relaxant responses in adjuvant-induced arthritis of the rat and to determine the effects of vitamin E administration on these changes. Arthritis was induced by a single intradermal injection of Freund's complete adjuvant into the paw. 26 days after the induction of arthritis, serum homocysteine levels and relaxant responses to acetylcholine and sodiumnitroprusside in thoracic aortas were evaluated. The relaxant responses to acetylcholine were decreased in aortas from arthritic rats, whereas the responses to sodiumnitroprusside were not significantly different when compared to the aortas from control rats. A significant increase was observed in serum homocysteine levels of the arthritic rats in comparison to those of controls. Vitamin E administration (100 mg/kg/day, i.m. for 26 days) to arthritic rats resulted in a significant increase in endothelium-dependent aortic responses to acetylcholine and a significant decrease in serum homocysteine levels with respect to the non-treated arthritic rats. However, in healthy rats, vitamin E treatment significantly decreased the acetylcholine-induced relaxant responses. We conclude that adjuvant-induced arthritis in the rat is associated with increased serum homocysteine levels and this is accompanied by a reduction in endothelium-dependent vascular responses in the thoracic aortas. Vitamin E treatment leads to normalization of the increased serum homocysteine levels and improves the endothelium-dependent relaxant responses in this experimental model.     

Morphine self-administration in the rat during adjuvant-induced arthritis

Rats injected with Freund's adjuvant develop a syndrome resembling human rheumatoid arthritis complete with paw swelling, edema and persistent pain. At the onset of pain, arthritic rats and their pain-free littermate controls (vehicle injection) were allowed to self-administer intravenous morphine (5.0 mg/kg/injection) in a 24 hr/day schedule. Self-injected morphine appeared to provide analgesia in arthritic rats as demonstrated by a decreased sensitivity to applied tail pressure. Arthritic rats self-inject significantly less morphine than pain-free animals. Injection of indomethacin, which alleviates the pain and inflammation of the adjuvant-induced disease, reduces, at least initially, morphine self-injection in the arthritic but not pain-free animals. As the adjuvant-induced inflammation and pain dissipated, arthritic rats rapidly began to increase opioid intake. The presence of persistent pain apparently reduces the addictive properties of morphine.     

对肾上腺素性心肌缺血模型大鼠相关指标的探讨

目的进一步探讨客观评价大鼠心肌缺血模型的指标。方法观察皮下注射10mg kg异丙肾上腺素(ISO)造成SD大鼠心肌缺血性损伤模型后心电图的变化、检测血清中肌酸激酶(CK)、乳酸脱氢酶(LDH)、游离脂肪酸(FFA)以及心肌组织的坏死面积、超氧化物歧化酶(SOD)、丙二醛(MDA)含量的变化。结果腹腔注射ISO后30s,大鼠心电图的J点开始降低,2min后缓慢回升,但20min后仍未回复到原来的水平,而且20min内各时间点与给药前比较,模型对照组大鼠的J点与生理盐水对照组比较,差异有显著性(P<0.05);T波则在注射异丙肾上腺素30s后开始下降,10min内两组的T波一直保持显著差异(P<0.05),而且注射异丙肾上腺素后30s(P<0.01)以及5min(P<0.05)与给药前比较,T波均有显著差异;模型对照组大鼠血清中CK、LDH、FFA以及心肌组织中MDA浓度均显著高于生理盐水对照组,心肌坏死面积与这些指标呈正相关关系,心肌组织中SOD浓度显著低于生理盐水对照组。结论J点可以作为评价此种动物模型的主要指标,T波可以作为辅助指标,应重点观察20min内心电图的变化;可以选择CK、LDH、FFA、SOD、MDA等生化指标以及心肌坏死面积等来探讨抗心肌缺血药物的作用机理。     

Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone.     

Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic rat

We examined the effect of adjuvant arthritis on the content of immunoreactive calcitonin gene-related peptide (iCGRP) in the dorsal root ganglia at L4-L6 levels and the spinal cord at a lumbar level in rats. Arthritis was induced by inoculating adjuvant into both hind-paws twice at a 10 day interval. In the arthritic rats 15 days after the first inoculation (day 15), the content of iCGRP was significantly increased in the dorsal root ganglia, with no change in the dorsal and ventral horns. The content in the dorsal root ganglia was still high on day 26 and had decreased by day 40. An intrathecal injection of colchicine (0.2 mg, 18 hr before killing) enhanced the increase of iCGRP in the dorsal root ganglia and decreased it in the dorsal horn of arthritic rats, although in noninoculated rats such treatment produced no significant changes in the content of iCGRP in both regions. The arthritis-induced increase in the content of iCGRP in the dorsal root ganglia was significantly reduced after treatment with the antiinflammatory analgesic, diclofenac sodium, in a dose of 3 mg/kg/day, PO for 10 days. Swelling and hyperalgesia in the hind-paw were depressed after such treatment. These results suggest that adjuvant arthritis with long-lasting inflammation with pain facilitates the turnover, especially biosynthesis, of CGRP in primary afferent neurons.     

Copper activation of superoxide dismutase in rat erythrocytes

Several lines of evidence suggested that copper can activate a preexisting pool of superoxide dismutase (SOD) apoprotein in erythrocytes from copper-deficient rats. First, feeding adequate copper to copper-deficient rats raised initially low erythrocyte SOD activities to normal values in under one-third the time needed to replace the entire red cell population. Moreover, copper injection (1 mg Cu/kg, sc) doubled erythrocyte SOD activity levels in 16 h. Since protein synthesis is restricted in mature erythrocytes, these results imply that copper activated apoSOD in vivo. Furthermore, injected copper raised SOD activity contents of both young and old erythrocytes. Neither dietary copper status nor copper injection influenced red cell SOD immunoreactive protein levels. In contrast, copper injection increased the amount of copper associated with the SOD activity peak region resulting from gel filtration of hemoglobin-free erythrocyte proteins on Sephadex G-75. Copper ions (3 microM) elevated SOD activity levels in vitro by 63% in 4 h in intact red cells from copper-deficient rats. No activation took place in lysed red cells from the same rats or in intact cells from copper-adequate rats. These results all suggest that copper can activate SOD apoprotein in erythrocytes by a specific, saturable process.     

Treatment of adjuvant-induced arthritis with the combination of methotrexate and probiotic bacteria <Emphasis Type="Italic">Escherichia coli</Emphasis> O83 (Colinfant®)

A certain relationship was observed between the gastrointestinal system, arthritis and immune system. Patients with rheumatoid arthritis have an altered microflora composition and disturbed intestinal defensive barrier. Effect of probiotic bacteria (Colinfant®; COL) with known favorable effect on intestinal microflora was determined on the methotrexate (MTX) treatment of adjuvant arthritis. Rats with adjuvant arthritis were administered methotrexate 0.5 mg/kg body mass 2-times weekly per os, COL 1 mL/kg body mass every second day per os, and a combination of MTX+COL for a period of 28 d from the immunization. Levels of serum albumin, body mass, changes in hind paw swelling, and arthrogram score were estimated in rats as variables of inflammation and destructive arthritis-associated changes. Treatment with MTX, as well as with the combination treatment with MTX+COL significantly inhibited both inflammation and destructive arthritis-associated changes. The combination treatment inhibited both the hind paw swelling and arthrogram score more remarkably than MTX alone; on the other hand, the difference between combination treatment and MTX alone was not significant. Treatment with COL alone had no effect on adjuvant arthritis in rats. Colinfant® can increase the preventive effect of MTX treatment in rat adjuvant arthritis by improving its antiarthritic effects.     

Treatment of experimental adjuvant arthritis with the combination of methotrexate and lyophilized Enterococcus faecium enriched with organic selenium

The efficacy of combination therapy with methotrexate (MTX) and probiotic bacteriaEnterococcus faecium enriched with organic selenium (EFSe) in rats with adjuvant arthritis was determined. Rats with adjuvant arthritis were given MTX (0.3 mg/kg 2-times weekly, orally); lyophilizedE. faecium enriched with Se (15 mg/kg, 5 d per week, orally); and a combination of MTX plus EFSe for a period of 50 d from the immunization. Levels of serum albumin, serum nitrite/nitrate concentrations, changes in hind paw swellling, arthrogram score, bone erosions, whole body bone mineral density (BMD) and bone mineral content (BMC) were assayed in the rats as variables of inflammation and destructive arthritis-associated changes. Treatment with MTX and with the combination MTX+EFSe significantly inhibited markers of both inflammation and arthritis. Significant differences in favor of combination therapy with MTX+EFSe as compared to MTX alone were seen in serum albumin concentration, hind paw swelling and arthrogram score. Reductions in radiographic scores were also more pronounced in the combination therapy group. Combination therapy, but not MTX alone, inhibited the reduction of BMD and BMC; treatment with lyophilized EFSe alone had no significant effect on adjuvant arthritis in rats. The potent therapeutic effect of low dosage MTX therapy in combination with lyophilized EFSe on adjuvant arthritis in rats was shown.     

Increased acetylcholinesterase activity in selected regions of rat brain after chronic (−)-Deprenyl administration

(−)-Deprenyl, 0.05, 1.0, 2.0, and 10.0 mg/kg body weight, was administered intraperitonially to Wistar rats for 30 days. The activity of acetylcholinesterase, and monoamine oxidase A and B were assayed in different brain regions. After the experimental period acetyl cholinesterase activity was found to be significantly increased in frontal cortex [P<0.001] and hippocampus [P<0.001] but not in striatum and brainstem at 0.1, 1.0, and 2.0 mg/kg dose, the maximum increase being at 0.1 mg/kg dose. Monoamine oxidase B activity was inhibited by more than 90% at 1.0, 2.0, and 10.0 mg/kg dose while 0.05 and 0.1 dose inhibited only about 55% and 70% respectively. Monoamine oxidase A activity was inhibited to more than 70% at 1.0 mg dose and to more than 90% at 2.0 and 10.0 mg/kg dose. At 0.05 and 0.1 mg/kg dose monoamine oxidase A activity was not significantly altered.     

Dual dose-related action of peripherally administered morphine on cold-stimulated thyrotropin secretion in male rats

Cold-induced increase of thyrotropin (TSH) release was found to be inhibited after 10 or 20 mg/kg morphine sulfate (MO) injected intraperitoneally 30 min before the transfer of adult male rats from 30 to 4 degrees C for 60 min (i.e. 90 min before sacrifice). In contrast, lower doses of MO such as 2.5 and 5 mg/kg were found to stimulate the cold-induced TSH release under the same conditions. Such a cold-induced TSH release stimulated by lower doses of MO was found to be inhibited by intraperitoneal injection of 2 or 4 mg/kg naloxone (NX) 30 min before MO injection (i.e. 120 min before sacrifice) in a dose-dependent manner, while the same doses of NX were without effect on the levels of TSH after higher doses of MO. It is suggested that these effects may depend on different sensitivities of various hypothalamic loci involved in mediating either a stimulation or inhibition of TSH release.     

Effects of Onosma armeniacum root extract on ethanol-induced oxidative stress in stomach tissue of rats

This study investigated the effects of Onosma armeniacum K. (Boraginaceae) root extract (AR-1) on ethanol-induced stomach ulcers, and on some oxidant and antioxidant parameters, in stomach tissue in rats. The results obtained showed that AR-1 significantly inhibited ethanol-induced ulcers at 25, 50, 100 and 200 mg/kg doses. We found that 50, 100 and 200 mg/kg doses of AR-1 inhibited ulcers more effectively than did ranitidine. AR-1 at doses of 25, 50, 100 and 200 mg/kg significantly prevented the decrease in total glutathione (tGSH) level which occurs in damaged stomach tissues of rats given ethanol (control group). Only a 100 mg/kg dose of AR-1 significantly increased the glutathione S-transferase (GST) level in stomach tissue compared to the control. All doses of AR-1 except the 25 mg/kg dose eliminated the decrease in the superoxide dismutase (SOD) level in the stomach tissue of rats given ethanol. While all doses of AR-1 decreased malondialdehyde (MDA) levels significantly; all doses AR-1 except 25 mg/kg decreased myeloperoxidase (MPO) levels significantly compared to the control. The effect of AR-1 on catalase (CAT) activity was insignificant at all doses. AR-1 significantly increased nitric oxide (NO) levels at 50, 100 and 200 mg/kg doses compared to the control. Our results indicate that the protection of some antioxidant mechanisms and the inhibition of some oxidant mechanisms have a role in AR-1's antiulcer effect mechanism.     

Benfotiamine Enhances Antioxidant Defenses and Protects against Cisplatin‐Induced DNA Damage in Nephrotoxic Rats

The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin‐induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8‐hydroxy‐2'‐deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin‐induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:398‐405, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21501     

Salubrious effect of Semecarpus anacardium against lipid peroxidative changes in adjuvant arthritis studied in rats

Oxygen derived free radicals are known to play an important role in the etiology of tissue injury in rheumatoid arthritis. The effect of milk extract of Semecarpus anacardium nuts at the dose level of 150 mg/kg body weight for 14 days on adjuvant arthritis was studied for gaining insight into the intrigue disease in relation to the lipid peroxidation and antioxidant defence system. Increased lipid peroxides' levels in both plasma and tissues (liver, kidney and heart) of adjuvant arthritis was significantly decreased by the administration of the drug. The antioxidant defence system studied in tissues of arthritic animals were altered significantly as evidenced by the decreased level of non-enzymatic antioxidants (GSH, vitamin E, vitamin C, NPSH and TSH) and enzymatic antioxidants (catalase and GPx except SOD). Administration of Semecarpus anacardium nut extract brings back the altered antioxidant defence components to near normal levels. These observations suggest that the diseased stat e of adjuvant arthritis may be associated with augmented lipid peroxidation and the administration of the drug may exert its antiarthritic effect by retarding lipid peroxidation and causing a modulation in cellular antioxidant defence system. (Mol Cell Biochem 175: 65–69, 1997)     

Effects of various drugs on thyrotropin secretion in rats

The effects of alpha-neoendorphin, kyotorphin, melatonin or diphenylhydantoin (DPH) on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) release in rats were studied. alpha-neoendorphin (1.0 mg/kg), kyotorphin (1.0 mg/kg), melatonin (2.5 mg/kg) or DPH (75 mg/kg) was injected iv or ip, and the rats were serially decapitated. TRH, TSH and thyroid hormone were determined by radioimmunoassay. The hypothalamic immunoreactive (ir-TRH) contents decreased significantly after melatonin injection, but not after alpha-neoendorphin, kyotorphin or DPH. The plasma ir-TRH concentrations decreased significantly after DPH injection, but not after alpha-neoendorphin, kyotorphin or melatonin. The plasma TSH levels decreased significantly in a dose-related manner with a nadir at 10 min. after melatonin, at 30 min. after DPH and at 40 min. after alpha-neoendorphin or kyotorphin injection. The plasma thyroid hormone levels did not change significantly after these drugs injection. The plasma ir-TRH and TSH responses to cold were inhibited by these drugs, but the plasma TSH response to TRH was not influenced. In the L-DOPA- or 5-hydroxy-tryptophan (5-HTP)-pretreated group, the inhibitory effect of alpha-neoendorphin or kyotorphin on TSH levels was prevented, but not in the haloperidol- or para-chloprophenylalanine (PCPA)- pretreated group. In the haloperidol- or PCPA-pretreated group, the inhibitory effect of melatonin on TSH levels was prevented, but not in the L-DOPA- or 5-HTP-pretreated group. These drugs alone did not affect plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after these drugs injection did not differ from that of the control.(ABSTRACT TRUNCATED AT 250 WORDS)     

白花蛇舌草对Ⅱ型胶原蛋白诱导的大鼠类风湿性关节炎的治疗作用

目的：探讨白花蛇舌草（HD）对Ⅱ型胶原蛋白诱导的大鼠类风湿性关节炎（CIA）的治疗作用。方法：取SD大鼠60只随机分为对照组10只、造模组50只,造模组于背部皮内注射Ⅱ型胶原乳剂建立CIA大鼠模型,采用大鼠关节炎评分法评价其模型是否复制成功。造模组再随机分为模型组、雷公藤多苷（GTW）6 mg/kg组、白花蛇舌草3、6、12 g/kg组,每组10只,每天灌胃给予相应的试剂。每周观察关节炎指数和痛阈,于连续干预28 d后,各组大鼠眼眶静脉取血,观察白细胞介素1β（IL-lβ）、肿瘤坏死因子-α（TNF-α）、前列腺素E₂（PGE₂）、核因子κB受体活化因子配体（RANKL）及护骨素（OPG）水平。结果：与对照组比较,模型组大鼠关节炎指数,血清IL-lβ、TNF-α、PGE₂、RANKL、OPG及RANKL/OPG水平均明显升高（P<0.05）,光照阈值明显降低（P<0.05）;与模型组比较,雷公藤多苷组、白花蛇舌草低、中、高剂量组关节炎指数,血清IL-lβ、TNF-α、PGE₂、RANKL、OPG及RANKL/OPG水平均明显降低（P<0.05）,光照阈值明显升高（P<0.05）。结论：白花蛇舌草可明显降低CIA模型大鼠关节炎指数,升高痛域阈值,下调IL-lβ、TNF-α、PGE₂、RANKL、OPG水平,从而有效的防治CIA。