羊肚菌免疫调节作用研究

观察DNFB诱导小鼠迟发型变态反应、血清溶血素测定（血凝法）、小鼠腹腔巨噬细胞吞噬鸡红细胞试验,结果表明,羊肚菌可以促进小鼠细胞免疫功能提高液免疫功能,促进小鼠体内抗体的产生,具有增强小鼠腹巨噬功能,是一种比较有效的免疫调节剂。     

灵芝孢子粉免疫调节作用研究

观察DNFB诱导小鼠迟发型变态反应、血清溶血素测定（血凝法）、小鼠腹腔巨噬细胞吞噬鸡红细胞试验,结果表明,灵芝了粉可以促进小鼠细胞免疫功能提高体液免疫功能,促进小鼠体内抗体的产生,具有增强小鼠腹腔巨噬细胞吞噬功能,是一种比较有效的免疫调节剂。     

壳聚糖载黄芪多糖纳米粒调节糖尿病小鼠免疫功能

研究低分散度壳聚糖载黄芪多糖纳米粒(LCA)对糖尿病(DM)小鼠免疫功能的影响。注射链脲佐菌素与环磷酰胺混合试剂建立DM合并免疫力低下小鼠模型,酶法制备低分散度壳聚糖,离子交联法制备低分散度壳聚糖纳米粒,超声包埋黄芪多糖制备药物对昆明小鼠灌胃,每天1次,连续30 d。ELISA法检测小鼠血清Ig M、Ig G与INF-γ的含量,碳粒廓清法测定非特异性免疫功能,耳肿胀法检测迟发型变态反应,MTT法检测脾淋巴细胞增殖率以反映细胞免疫功能。结果显示灌胃350 mg/(kg·d)LCA显著提高血清Ig M、Ig G的分泌,显著降低INF-γ表达量,增强碳粒廓清率,提高小鼠迟发型变态反应(DTH),改善脾淋巴细胞增殖反应。适当剂量的低分散度壳聚糖载黄芪多糖纳米粒能提高DM小鼠体液免疫、非特异性免疫及细胞免疫功能,且效果优于纯黄芪多糖。     

猴头菌丝多糖降血糖作用研究

目的:研究猴头菌丝多糖的降血糖作用。方法:以液体发酵生产的猴头菌丝体为原料,经热水浸提、浓缩、酒精沉淀获得菌丝粗多糖;以常规降糖药物格列本脲为阳性治疗对照,通过四氧嘧啶诱发小鼠糖尿病的预防试验,比较猴头菌丝多糖各剂量与格列本脲的降血糖效果。结果:猴头菌丝多糖得率为7.14%,粗多糖再经Sevage法去除蛋白质,获得猴头菌丝精多糖(HMP),得率为10.92%;猴头多糖高、中、低三个剂量均能有效的对抗四氧嘧啶诱发的高血糖;其中,高剂量的降血糖作用与格列本脲相比,差异极显著。结论:猴头菌丝多糖对四氧嘧啶型高血糖模型小鼠有降血糖作用,作用效果优于格列本脲,对糖尿病小鼠的胰腺具有一定的保护作用。     

卡介苗溶菌黏膜免疫调理剂对激活荷瘤小鼠免疫功能的研究

观察卡介苗溶菌黏膜免疫调理剂对荷瘤小鼠免疫功能的激活。将SPF小鼠分组后用黑色素瘤B16和肝癌实体瘤H22感染,随后以灌胃途径引入本调理剂,分别发现它能促进荷瘤小鼠血清溶菌酶含量上升和T细胞介导的迟发型变态反应增强。试验结果表明,卡介苗溶菌黏膜免疫调理剂对荷瘤小鼠有升高其血清溶菌酶含量和增强迟发型变态反应的作用。     

一种双歧杆菌胞外多糖免疫调节功能研究

根据保健食品功能评价规范?功能学评价程序研究一种双歧杆菌胞外多糖(Bifidobacterium spp. exopolysaccharide, EPS)的免疫调节功能。通过脾淋巴细胞增殖反应、绵羊红细胞诱导小鼠迟发型变态反应(DTH)、血清溶血素测定以及巨噬细胞吞噬实验探讨该EPS的免疫调节活性。EPS分别以高、中、低剂量组连续口服给药10天, 结果发现低剂量的EPS[100 mg/(kg·d)]可以促进脾淋巴细胞增殖; 高、中、低剂量对绵羊红细胞诱导的小鼠迟发型变态反应均无促进作用; 但是, EPS 高、中、低剂量组均能明显提高小鼠血清半数溶血值HC50以及增强小鼠腹腔巨噬细胞吞噬鸡红细胞的吞噬能力。根据规范可知, 该双歧杆菌EPS 具有一定的免疫调节活性。     

阿泰宁对抗生素诱导的大鼠肠道菌群失调和免疫功能的影响

目的探讨阿泰宁对抗生素诱导的大鼠肠道菌群失调的恢复作用以及免疫功能的影响。方法通过给大鼠灌服抗生素诺氟沙星胶曩造成肠道菌群失调模型,然后给予阿泰宁治疗,随后进行肠道菌群分析、迟发型变态反应试验、NK细胞活性测定和T淋巴细胞转化率测定等。结果抗生素组肠道菌群失调,NK细胞活性较正常组显著降低（P〈0．01）,经阿泰宁治疗后,肠道菌群恢复平衡,在迟发型变态反应试验中,阿泰宁组足跖增厚显著高于正常组和抗生素组（P〈0．05）,T淋巴细胞转化率较正常组和模型组显著升高（P〈0．01）。结论阿泰宁能够有效恢复抗生素引起的肠道菌群失调,并能有效提高免疫。     

黄原胶（Xanthan Gum）对小鼠免疫功能的影响

给小鼠每天分别灌胃10,2和0．4μg/g的黄原胶溶液14d,研究观察黄原胶对小鼠脾脏和胸腺、IgM－PFC反对小鼠迟发型变态反应（DTH）的影响。实验发现,黄原胶对小鼠脾脏和胸腺增重及DTH的影响未见明显变化,而使小鼠的IgM-PFC显著增加。实验结果表明,黄原胶对增加小鼠脾脏和胸腺重量及增强小鼠细胞免疫功能作用不大,而对小鼠的体液免疫功能具有明显的增强作用。     

植物乳杆菌P-8对小鼠免疫功能的调节作用研究

摘要 目的：不同类型的益生菌株免疫调节功能各异。本文旨在评价植物乳杆菌P-8（Lactobacillus plantarum P-8）对小鼠免疫功能的调控作用及机制。方法：C57BL/6J小鼠每日灌胃给予不同剂量的植物乳杆菌P-8（0. 25 mg/kg、0.5 mg/kg、1.5 mg/kg）,连续30天,记录小鼠一般情况。给药结束后处死动物,测定小鼠脏器/体重比;小鼠碳廓清实验、小鼠腹腔巨噬细胞吞噬鸡红细胞实验评价各组小鼠的单核-巨噬细胞功能;血清溶血素测定、抗体生成细胞实验评价各组小鼠的体液免疫功能;脾淋巴细胞转化实验、迟发型变态反应实验评价各组小鼠的细胞免疫功能;NK细胞的活性测定实验评价小鼠的NK细胞活性。结果：与对照组相比,低、中、高剂量组植物乳杆菌P-8对小鼠脏器/体重比值差异无统计学意义（P>0.05）;且植物乳杆菌P-8可显著提高小鼠的碳廓清能力、小鼠腹腔巨噬细胞吞噬鸡红细胞能力、半数溶血值、二硝基氟苯诱导的小鼠迟发型变态反应及NK细胞活力（P均<0.05）。结论：植物乳杆菌P-8可通过提高单核-巨噬细胞功能、体液免疫功能、细胞免疫功能及NK细胞活力增强小鼠的免疫功能。     

重组铜绿假单胞菌外毒素结构域Ia片段的佐剂功效研究

采用分子克隆技术,将铜绿假单胞菌PA103株编码的外毒素结构域Ia(Domain Ia)的基因重组于原核表达载体pET-42b( )上,构建了pET-EPA103蛋白表达载体。转化感受态大肠杆菌DE3。经IPTG诱导表达,初步纯化表达蛋白,用以免疫BALB／c纯系小鼠。制备小鼠脾淋巴细胞悬液,经刀豆素A(ConA)刺激后,用MTT比色法检测特异性淋巴细胞增殖反应。通过rEPA皮下注射BALB／c小鼠耳廓,诱导小鼠迟发型过敏反应(DTH)。采用特异性淋巴细胞增殖反应和DTH试验来检测pET-EPA103表达蛋白所引起的小鼠细胞免疫应答水平,淋巴细胞增殖情况与DTH均可间接反映细胞免疫应答水平,进而评价重组铜绿假单胞菌外毒素(rEPA)Domain Ia蛋白片段的佐剂功效。     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.     

Hypoglycemic benefit and potential mechanism of a polysaccharide from Hericium erinaceus in streptozotoxin-induced diabetic rats

In this study, the hypoglycemic effect and possible mechanism of a polysaccharide, HEP-C, isolated from the fruit body of Hericium erinaceus were evaluated in streptozotoxin (STZ)-induced diabetic rats. Compared with the untreated STZ-induced diabetic rats, the supplements with HEP-C (150 and 300 mg/kg body weight [BW]) could significantly and dose-dependently relieve BW loss and organ injures, reduce fasting blood glucose, enhance glucose tolerance, alleviate hepatic function and serum lipid metabolism, elevate antioxidant enzyme activities, and suppress lipid peroxidation, which contributed to its potent hypoglycemic benefit. Liver histopathological observation revealed that HEP-C could effectively attenuate the deteriorated hepatic lesions in STZ-induced diabetic rats. HEP-C with potent hypoglycemic effect positively mediated glycogen synthesis by activating the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. In summary, these results suggested that HEP-C, as a new dietary functional food or therapeutic agent, exhibited great potential for the prevention and treatment of diabetes mellitus and its complications.     

Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice) reverses learning and memory deficits in diabetic rats

Cognitive impairment occurs in diabetes mellitus. Glabridin as a major active flavonoids in Glycyrrhiza glabra (licorice) improves learning and memory in mice. In the present study, we investigated the effect of chronic treatment with glabridin (5, 25 and 50 mg/kg, p.o.) on cognitive function in control and streptozotocin (STZ)-induced diabetic rats.Animals were divided into untreated control, glabridin-treated control (5, 25 and 50 mg/kg), untreated diabetic and glabridin treated diabetic (5, 25 and 50 mg/kg) groups. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning (PAL) and memory was assessed 30 days later. Diabetes caused cognition deficits in the PAL and memory paradigm. While oral glabridin administration (25 and 50 mg/kg) improved learning and memory in non-diabetic rats, it reversed learning and memory deficits of diabetic rats. Low dose glabridin (5 mg/kg) did not alter cognitive function in non-diabetic and diabetic groups. Glabridin treatment partially improved the reduced body weight and hyperglycemia of diabetic rats although the differences were not significant. The combination of antioxidant, neuroprotective and anticholinesterase properties of glabridin may all be responsible for the observed effects. These results show that glabridin prevented the deleterious effects of diabetes on learning and memory in rats. Further studies are warranted for clinical use of glabridin in the management of demented diabetic patients.     

负重爬梯与有氧跑台运动对糖尿病大鼠学习记忆能力的影响及其机制探讨

目的：研究负重爬梯与有氧跑台运动对糖尿病大鼠学习记忆能力的改善效果并探索其可能分子机制。方法：40只雄性大鼠,随机分为正常对照组（NC）、糖尿病对照组（DC）、糖尿病负重爬梯组（DL）和糖尿病有氧跑台组（DA）,以单次腹腔注射链脲佐菌素构建糖尿病大鼠模型。DL组在晚上进行负重爬梯训练,10次/组×3组/天,每次间歇2 min,6天/周×6周;DA组在同一时间进行20 m/min的跑台训练,30 min/d。于造模成功和运动干预结束后采用Morris水迷宫检测大鼠的学习记忆能力;第2次水迷宫测试结束后断颈处死大鼠,采用RT-QPCR法检测大鼠海马内脑源性神经营养因子（BDNF）、TRKB、CREB mRNA表达水平。结果：与NC组相比,DC组大鼠海马BDNF、CREB基因表达显著下降,学习记忆能力显著降低。与DC组相比,DL和DA组大鼠海马BDNF、CREB基因表达显著上调,学习能力显著提高;DL大鼠海马TrkB基因显著上调,大鼠空间记忆能力显著改善,而DA组大鼠海马TrkB基因无显著变化,大鼠空间记忆能力无改善,与DA组相比,DL组大鼠海马TRKB、CREB基因显著上调。结论：有氧跑台运动与负重爬梯运动介导BDNF/TrkB/CREB信号通路对糖尿病大鼠的学习能力均有促进作用,而负重爬梯运动对糖尿病大鼠记忆能力的改善优于有氧运动方式。     

Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver

The aim of this study was to examine the effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver of streptozotocin (STZ)-induced diabetic rats. Twenty-seven rats were randomly divided into three groups: group I, control non-diabetic rats (n = 9); group II, STZ-induced, untreated diabetic rats (n = 8); group III, STZ-induced, CAPE-treated diabetic rats (n = 10), which were intraperitoneally injected with CAPE (10 microM kg(-1) day(-1)) after 3 days followed by STZ treatment. The liver was excised after 8 weeks of CAPE treatment, the levels of malondialdehyde (MDA) and the activities of SOD, CAT, and GSH-Px in the hepatic tissues of all groups were analyzed. In the untreated diabetic rats, MDA markedly increased in the hepatic tissue compared with the control rats (p < 0.0001). However, MDA levels were reduced to the control level by CAPE. The activities of SOD, CAT, and GSH-Px in the untreated diabetic group were higher than that in the control group (p < 0.0001). The activities of SOD and GSH-Px in the CAPE-treated diabetic group were higher than that in the control group (respectively, p < 0.0001, p < 0.035). There were no significant differences in the activity of CAT between the rats of CAPE-treated diabetic and control groups. Rats in the CAPE-treated diabetic group had reduced activities of SOD and CAT in comparison with the rats of untreated diabetic group (p < 0.0001). There were no significant differences in the activity of GSH-Px between the rats of untreated diabetic and CAPE-treated groups. It is likely that STZ-induced diabetes caused liver damage. In addition, LPO may be one of the molecular mechanisms involved in STZ-induced diabetic damage. CAPE can reduce LPO caused by STZ-induced diabetes.     

Vanadium-enriched chickpea sprout ameliorated hyperglycemia and impaired memory in streptozotocin-induced diabetes rats

Vanadium compounds have been recognized for their hypoglycemic effects; however, potential short and long-term vanadium toxicity has slowed the acceptance for therapeutic use. In the present work, three batches of vanadium-enriched chickpea sprout (VCS) were prepared by incubating chickpea seeds in presence of 200, 100, and 50 mug/ml of sodium orthovanadate (SOV). The effects of oral administration of chickpea sprout (CS) and VCS food for 8 weeks on streptozotocin-induced (STZ) diabetic rats were investigated. Both CS and VCS food was found to ameliorate some hyperglycemic symptoms of the diabetic rats, i.e. improve lipid metabolism, decrease blood glucose level, prevent body weight loss, and reduce impairment of diabetic related spatial learning and memory. Serum insulin was substantially elevated in treated diabetic rats, which is probably one important reason for the hypoglycemic effect. Compared with CS alone, VCS100 food exhibited remarkably enhanced effectiveness in alleviating diabetes induced hyperglycemia and memory loss. Moreover, vanadium-enriched chickpeas appeared to abolish the vanadium induced toxicity associated with administration of this metal for diabetes during the 8-week study period. This study suggested further work of the vanadium speciation in CS and novel hypoglycemic mechanism for the antidiabetic activity of vanadium agents. Vanadium containing (VCS) food could be a dietary supplement for the diabetic status.     

Primary study on the hypoglycemic mechanism of 5rolGLP-HV in STZ-induced type 2 diabetes mellitus mice

5rolGLP-HV is a promising dual-function peptide for the treatment of diabetes and thrombosis simultaneously. For investigating the therapeutic mechanism of 5rolGLP-HV for type 2 diabetes mellitus (T2DM), STZ-induced diabetic mice were established and treated with 5rolGLP-HV. The results showed that daily water and food intake, blood glucose, serum and pancreatic insulin levels significantly decreased after 5rolGLP-HV treatment with various oral concentrations, and 16 mg/kg was the optimal dose for controlling diabetes. 5rolGLP-HV treatment decreased the MDA levels and the T-SOD activity in serum and pancreatic of diabetic mice (but not up to significant difference), and significantly increased the expression of signal pathways related genes of rolGLP-1, also the density of insulin expression and the numbers of apoptosis cells in islets of diabetic mice were significantly decreased in comparison to the negative diabetic mice. These effects above may be clarified the hypoglycemic mechanisms of 5rolGLP-HV, and 5rolGLP-HV may be as a potential drug for diabetes in future.     

Role and differential expression of calpastatin mRNA and protein in cultured cardiomyocytes exposed to hypoxic stress

This study investigated the beneficial effects and mechanism of action of the juice of Momordica charantia in streptozotocin (STZ)-induced diabetes mellitus in rats. Diabetes mellitus was associated with significant (p < 0.01) time course reductions in body weight, plasma insulin and the number of insulin positive cells per islet and significant (p < 0.01) time course elevation in blood glucose and osmolarity and systolic blood pressure compared to age-matched healthy controls. Oral intake of M. charantia juice by STZ-induced diabetic rats partially reversed all the diabetes-induced effects measured. Daily oral administration of M. charantia juice to STZ-induced diabetic rates significantly (p < 0.01) reduced the Na+- and K+-dependent absorptions of glucose by the brush border membrane vesicles of the jejunum compared to the responses obtained in STZ-induced diabetic rat. Either insulin (100 MM) or the fruit juice lyophilised extract (5 microg x ml(-1)) can stimulate 14C-D-glucose uptake in L6 myotubes. These effects were completely blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. High concentrations (10-200 microg x ml(-1)) of M. charantia juice extract inhibited 14C-D-glucose uptake in L6 myotubes compared to the control response. The effect of M. charantia treatment was also investigated on myelinated fibre abnormalities in the tibial nerve of STZ-induced diabetic and control rats. The results show that diabetes was associated with significant (p < 0.05) reduction in the mean cross-sectional myelinated nerve fibres, axonal area, myelin area and maximal fibre area compared to end controls. Treatment of STZ-induced diabetic rats with M. charantia juice normalised the structural abnormalities of peripheral nerves. The results indicate that M. charantia can exert marked beneficial effects in diabetic rats, and moreover, it can regulate glucose uptake into jejunum membrane brush border vesicles and stimulate glucose uptake into skeletal muscle cells similar to the response obtained with insulin.     

Role of insulin signaling impairment,adiponectin and dyslipidemia in peripheral and central neuropathy in mice

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype.KEY WORDS: Glucose, High-fat diet, Insulin, Neuropathy