半夏泻心汤治疗慢性萎缩性胃炎的临床分析

目的观察半夏泻心汤治疗慢性萎缩性胃炎的临床效果。方法选择我院2014年1~12月收治的106例慢性萎缩性胃炎患者为研究对象,随机分为对照组和治疗组各53例。对照组采用常规西药治疗,治疗组采用半夏泻心汤治疗,比较两组患者的幽门螺杆菌(Hp)感染情况、临床疗效及不良反应发生率。结果治疗组Hp转阴率(81.1%)明显高于对照组(50.0%),治疗总有效率(94.3%)显著高于对照组(81.1%),不良反应发生率(0.0%)明显低于对照组(11.3%),差异均具有统计学意义(均P0.05)。结论半夏泻心汤治疗慢性萎缩性胃炎的效果好,安全性高,并发症少,值得临床推广使用。     

甘草泻心汤对抗生素诱导肠道菌群失调小鼠 肠道主要菌群及sIgA的影响

摘要：目的 探索甘草泻心汤对抗生素诱导肠道菌群失调小鼠肠道主要菌群及sIgA的影响。方法 将40只实验小鼠随机分为4组：正常对照组、模型对照组、甘草泻心汤组和思连康组,每组10只,给予除正常对照组以外的其他组小鼠盐酸林可霉素7 d进行造模。造模成功后,甘草泻心汤组小鼠给予10.16 g/kg体重的甘草泻心汤浓缩液灌胃,思连康组小鼠给0.68 g/kg思连康灌胃。正常对照组及模型对照组小鼠给予10 mL/kg的生理盐水代替,14 d后收集小鼠新鲜粪便采用平皿计数法进行肠道菌群检测,并采用免疫组化法检测肠道sIgA的表达情况。结果 甘草泻心汤以及思连康均能降低肠道菌群失调小鼠肠道内大肠埃希菌、肠球菌的数量,增加双歧杆菌、乳杆菌的数量,促进肠道内sIgA的表达,甘草泻心汤疗效优于思连康（P＜0.001）。结论 甘草泻心汤及思连康均能够纠正小鼠肠道菌群失调状态,甘草泻心汤疗效优于思连康,其调节机制可能是通过促进肠道内sIgA的表达来实现的。     

半夏和滴水珠抗五步蛇毒中毒作用的实验研究

目的研究滴水珠与半夏生药及其提取物抗五步蛇毒的作用。方法将ICR小鼠随机分为半夏生药组、半夏醇提物组、滴水珠生药组、滴水珠醇提物组、空白对照组、阳性对照组及模型组,各组小鼠均灌胃给药7天,并观察各给药组小鼠的体重变化情况;在末次给药1h后于小鼠腹腔注射五步蛇毒,观察各组小鼠的中毒表现,并统计各组小鼠的死亡率,比较各组小鼠的肝脏指数、脾脏指数及胸腺指数,并对各组小鼠血浆纤维蛋白原（FIB）、血浆凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血酶时间（APTT）以及血小板（PLT）、红细胞（RBC）和白细胞（WBC）计数进行比较。结果半夏和滴水珠醇提物、半夏和滴水珠生药均可降低五步蛇毒中毒小鼠的死亡率,对五步蛇毒引起的小鼠PT、TT、APTT上升和FIB下降具有显著的抑制作用,与模型组相比P〈0.05;并可影响五步蛇毒中毒小鼠外周血血小板（PLT）、红细胞（RBC）和白细胞（WBC）计数,与模型组相比P〈0.05。但滴水珠和半夏生药可引起小鼠体重下降,并影响肝脏、胸腺和脾脏指数,与空白对照组相比P〈0.05。结论半夏和滴水珠醇提物及半夏和滴水珠生药均具有一定的抗五步蛇毒作用,乙醇提取能降低半夏和滴水珠的毒性。     

束缚应激对D-氨基半乳糖联合脂多糖诱导小鼠肝损伤的保护作用

目的探讨束缚应激对D-氨基半乳糖联合脂多糖（D–galactosamine and lipopolysaccharide combination,D＋L）诱导的小鼠肝损伤的保护作用。方法正常BALB/c小鼠随机分为正常对照组（con）、应激对照组（str）、模型组（D＋L）、束缚应激组（D＋L＋str）。con组小鼠常规饲养;str组小鼠给予定时定量的束缚应激;D＋L组小鼠腹腔注射D-氨基半乳糖和脂多糖的混合溶液,1次/2天;D＋L＋str组小鼠腹腔注射等量D＋L混合液后,给予与str组相同的束缚应激。第8周,各组小鼠取血检测血清AST、ALT,肝脏固定后HE及Masson染色观察小鼠肝脏结构、细胞形态及纤维化程度。结果第8周D＋L＋str组与D＋L组小鼠相比,血清ALT和AST显著降低（P〈0.01）,AST/ALT显著增高（P〈0.01）;HE及Masson染色显示,D＋L组小鼠肝小叶结构紊乱,出现结节性增生及大量上皮细胞核浓缩、溶解、坏死,枯否氏细胞浸润,而D＋L＋str组未见明显病理变化;纤维化程度评分显示,D＋L＋str组与D＋L组小鼠相比,病理评分与纤维显色吸光度值均显著降低（P〈0.05）。结论束缚应激对D＋L诱导的小鼠肝损伤具有一定保护作用。     

半夏泻心汤治疗糖尿病胃轻瘫的作用机制

本研究探讨ICC(胃肠道间质细胞)和Cx43(缝隙连接蛋白)在半夏泻心汤治疗豚鼠糖尿病胃轻瘫的过程中所起的作用及机制。制备半夏泻心汤含药血清并建立糖尿病胃轻瘫豚鼠模型。处死豚鼠并取材胃标本后免疫组化染色标记c-Kit和Cx43抗体,显微镜下观察并比较实验各组豚鼠ICC和Cx43的数量及变化,并通过透射电镜观察ICC的超微结构变化。结果显示:半夏泻心汤含药血清能明显增加糖尿病胃轻瘫豚鼠ICC的数量,并能修复其受损的超微结构;半夏泻心汤治疗组Cx 43阳性表达密集分布在胃体和胃窦部环形肌层中,阳性表达的强弱与ICC的阳性分布具有一致性。由此,我们可以推断出以下结论:ICC的数量显著减少并发生变性是发生糖尿病胃轻瘫的一个重要原因,半夏泻心汤含药血清能明显增加豚鼠ICC的数量并修复其受损结构,进而增强其胃动力并恢复功能,从而起到治疗豚鼠糖尿病胃轻瘫的作用。     

复合因素建立亚健康小鼠模型

目的:复合因素建立与临床症状相似的亚健康小鼠模型。方法:采用强迫游泳、睡眠剥夺、装管束缚、夹鼠尾应激建立亚健康小鼠模型,通过小鼠外观、行为学数据及病理检测鉴定模型是否成功。结果:造模结束后,模型组小鼠外观、体重、自主活动量、避暗次数、绝望时间、力竭游泳时间与对照组小鼠相比差异显著(P0.05),病理结果显示模型组小鼠未见异常。结论:复合因素成功建立亚健康小鼠模型。     

甘露寡糖及壳聚糖对四氧嘧啶致糖尿病小鼠血糖血脂的影响

目的研究甘露寡糖和壳聚糖对四氧嘧啶致实验性糖尿病小鼠血糖、血脂的影响。方法随机选取70只健康小鼠,10只为正常对照组,其余由腹腔注射四氧嘧啶(150mg/kg),建立糖尿病模型,用快速血糖仪测血糖值,血糖值>11.1mmol/L的小鼠则为造模成功小鼠,将造模成功的小鼠随机分成5组,每组各12只。分别为模型对照组,高剂量、低剂量甘露寡糖处理组,高剂量、低剂量壳聚糖处理组。高低剂量分别以400mg/kg和200mg/kg糖溶液进行灌胃,空白组和模型组灌予等体积的生理盐水。12d后测定小鼠血清中血糖(GLU)、总胆固醇(CHO)、高密度脂蛋白胆固醇(HDL-C)和甘油三酯(TG)的浓度。结果甘露寡糖和壳聚糖使糖尿病小鼠的血糖与模型对照组相比有显著的降低,CHO和TG的浓度也显著降低,HDL-C显著升高;且高剂量的甘露寡糖和壳聚糖的降血糖、血脂效果优于低剂量。     

硬枝碱蓬多糖对免疫抑制小鼠血清中NO含量及NOS活性的影响

采用氢化可的松皮下注射小鼠建立免疫抑制模型,观察不同浓度硬枝碱蓬多糖(100、200和400mg/kg·d)灌服小鼠后(模型对照组灌服等体积生理盐水),对免疫抑制小鼠血清中NO含量及TNOS、iNOS活性的影响。结果表明:3个试验组免疫抑制小鼠血清中NO含量及TNOS、iNOS活性均明显降低。其中,硬枝碱蓬多糖低、中浓度组iNOS活性显著低于模型对照组(P<0.05),高浓度组iNOS活性极显著低于模型对照组(P<0.01);硬枝碱蓬多糖低、中、高浓度组NO含量及TNOS活性与模型对照组相比差异均极显著(P<0.01),且呈现明显的浓度依赖效应。结果提示,硬枝碱蓬多糖可通过抑制NOS并最终抑制NO的细胞毒性作用而对正常组织细胞发挥保护作用,并进一步增强小鼠的免疫力。     

应激致免疫功能降低动物模型的建立

目的为探讨应激对免疫系统损伤的作用机制,建立了两种不同的应激导致机体免疫功能降低的动物模型。方法将小鼠分为三组,束缚应激组、热应激组和正常对照组,分别用束缚和高温刺激使小鼠处于应激状态,应激结束后将各组小鼠均分为两部分,一部分感染细菌,比较两种应激状态下小鼠与正常小鼠的死亡率,另一部分摘取脾脏,计算脾脏重量指数,制作脾脏病理切片,观察其组织病理学变化。结果注射大肠埃希菌后束缚应激组和热应激组小鼠死亡率显著高于正常对照组小鼠(P<0.005),束缚应激组和热应激组小鼠死亡率无明显差异(P>0.05)。束缚应激组小鼠和热应激组小鼠脾脏重量指数均较正常对照组明显降低(P<0.05),组织病理学观察显示束缚应激组和热应激组小鼠脾脏切片病理学改变相似,白髓比例减小,脾小体有不同程度的缩小、分布及结构不规则。结论本实验建立的应激导致小鼠免疫功能降低的动物模型,其免疫功能降低与脾脏变化间存在构效关系,与应激的类型关系不大。     

牛樟芝固态发酵产物的降胆固醇作用

本实验主要探究牛樟芝(S-29)固态发酵产物对高脂饮食小鼠胆固醇调节的影响。小鼠随机分为正常组、高脂模型组、护肝片阳性对照组、固态发酵组及液态发酵组;小鼠经高脂饲料喂养6周,相应物质灌胃4周。检测小鼠血清及肝脏相关指标; q-PCR检测胆固醇代谢相关基因的mRNA表达量。结果表明,与模型组比较,固态发酵组小鼠血清游离脂肪酸(NEFA)及谷丙转氨酶(ALT)浓度显著降低,分别降低了38. 5%和40. 7%;肝脏总胆固醇(TC)浓度显著降低,降低了23. 5%;低密度脂蛋白受体(LDL-R)的mRNA表达量显著增加,增加了3. 6倍。结果证明,牛樟芝固态发酵产物具有较好的降胆固醇作用,其主要机制可能是通过上调LDL-R基因的表达,以促进胆固醇的分解代谢,进而降低小鼠体内胆固醇浓度。     

The effect of recaging into groups or into isolation on the pituitary adrenal response to immobilization of different age groups of C57BL/6J mice

Although there is evidence which suggests that age and social environment are significant variables in all experiments dealing with stress in intact animals, there is relatively little information available on the manner in which these variables interact to influence the pituitary adrenal response to stress. Inbred mice of strain, C57BL/6J, of 3 different age groups (49, 255 and 720 days) were subjected to a brief immobilization stress 24 hours subsequent to regrouping them 1, 2 or 4 per cage. Plasma corticosterone concentration was measured by radioimmunoassay prior to and 15 minutes after immobilization or 60 minutes after treatment with ACTH. It was found that preimmobilization levels of corticosterone and increments in corticosterone in response to ACTH treatment were smaller in 255 day than in 49 or 720 day old mice and that preimmobilization corticosterone levels of control and recaged 49 and 255 day old mice were similar. In 49 day old mice, recaging increased the immobilization evoked increment in corticosterone, but in 255 and 720 day old mice recaging in groups or pairs did not change the immobilization evoked response. However, recaging of 720 day old mice in isolation resulted in a decrease in the immobilization evoked increment. Therefore, it appears that the act of transfer itself increased the pituitary adrenal function in the 49 day old mice while, in the oldest mice, isolation itself reduced pituitary adrenal activity. Finally, it appears that in the 255 day old mice, recaging is only a minor stress since after 24 hours′ there is no evidence of elevated steroid levels.     

Single limb immobilization model for bone loss from unloading

Hindlimb suspension is the most used model for inducing bone loss from unloading but requires a separate ground control group. This control group cannot be used for genetic studies involving outbred mice. In this study, we evaluated a single limb immobilization (SLI) model for inducing bone loss from unloading, with the contralateral limb from the same animal used as a control. Male 10-week old C57Bl/6J mice had one limb immobilized for one, two, or three weeks. Subsequently, an additional group of male 16-week old C57Bl/6J mice had one limb immobilized for three weeks. SLI resulted in decreased tibial trabecular BV/TV, Tb Th, and Tb N compared to contralateral limbs in young mice. Femoral trabecular BV/TV, Tb Th, Tb N, and femoral cortical area fraction were also decreased. Mechanical properties were not affected after three weeks. In adult mice, femoral trabecular BV/TV, Tb Th, and Tb N were decreased. Femoral stiffness, ultimate stress, and Young’s modulus were decreased. Bone properties decreased by SLI were also decreased by hindlimb suspension previously. The results suggest SLI can be an effective model for inducing bone loss in growing and adult mice after three weeks of immobilization.     

Immobilization stress induces c-Fos accumulation in liver

Acute stress-induced injury in tissues has been revealed by both biochemical markers in plasma and microscopy. However, little is known of the mechanisms by which tissue integrity is restored. Recently, induction of early response genes such as c-fos has been reported in the heart and stomach of immobilized animals. Herein, we show that immobilization stress in mice increased plasma alanine aminotransferase activity, a marker of liver damage. c-Fos protein accumulation in liver was induced by stress after 20 minutes of immobilization and persisted for 3 hours. Immobilization also induced the release of epidermal growth factor (EGF) from submandibular salivary glands and a transient increase in EGF concentration in plasma. Although EGF administration induced a 2.5-fold increase in c-Fos mass in the liver of anesthetized mice, sialoadenectomy (which abolished the effect of immobilization on plasma EGF) did not affect the stress-induced rise in plasma alanine aminotransferase activity or liver c-Fos accumulation. Therefore, we conclude that immobilization stress induces c-Fos accumulation in liver and that this effect is not triggered by the increase in plasma EGF concentration.     

Influences of Different Stress Models on the Antioxidant Status and Lipid Peroxidation in Rat Erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 &#45 2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.     

Influences of different stress models on the antioxidant status and lipid peroxidation in rat erythrocytes

The aim of this study was to investigate the influences of different stress models on the antioxidant status and lipid peroxidation (LPO) in erythrocytes of rats. Swiss-Albino female rats (3 months old) were used in this study. Rats were randomly divided into the following four groups; control group (C), cold stress group (CS), immobilization stress group (IS) and cold+immobilization stress group (CS+IS). Control group was kept in an animal laboratory (22 ±2°C). Rats in CS group were placed in cold room (5°C) for 15 min/day for 15 days. Rats in IS group were immobilized for 180 min/day for 15 days. Rats in CS+IS group were exposed to both cold and immobilization stresses for 15 days. At the end of experimental periods, the activities of glucose-6-phosphate dehydrogenase (G-6-PD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and concentration of reduced glutathione (GSH) were measured. LPO was determined by measuring the contents of thiobarbituric acid-reactive substances (TBARS). Cu,Zn-SOD activity and TBARS concentration were increased after cold and immobilization stresses, but CAT and GSH-Px activities and GSH levels were decreased. Immobilization stress decreased the activity of G-6-PD. The activities of G-6-PD, CAT and GSH-Px, and the level of GSH were lower in CS+IS group than in the control group. Cu,Zn-SOD activity and TBARS levels were increased in CS+IS group when compared with the control group. From these findings, three stress models are thought to cause oxidative stress.     

Effects of chronic immobilization stress on biokinetics and dosimetry of 67 Ga in a murine model

The aim of this work is to determine the effect of chronic immobilization stress on kinetics and dosimetry of 67Ga in a mouse model. A control group (CG) and a stress group (SG), each with 15 mice, were included in the study, and the latter group was subjected to a chronic immobilization stress model 2 h daily for 14 consecutive days. At day 13, 67Ga-citrate was administered intraperitoneally (11.24 ± 0.44 MBq) to each mouse. Then, sets of three mice were obtained sequentially at 24, 36, 48, 60 and 72 h, in which the radionuclide activity was measured with an activity counter. The 67Ga biokinetic data showed a fast blood clearance in the SG, with a mean residence time of 0.06 h. The calculated mean radiation absorbed doses were: liver (2.45 × 10−03 Gy), heart (3.17 × 10−04 Gy) and kidney (1.88 × 10−04 Gy) in the SG. The results show that stress reduced weight gain by approximately 13% and also increased adrenal gland weight by 26%. On the other hand, chronic stress accelerates 67Ga clearance after 24 h compared to normal conditions. It is concluded that murine organisms under chronic immobilization stress have higher gallium-67 clearance rates, decreasing the cumulated activity and absorbed dose in all organs.     

Deficiency of inducible nitric oxide synthase attenuates immobilization-induced skeletal muscle atrophy in mice

The present study examined the effects of inducible nitric oxide synthase (iNOS) deficiency on skeletal muscle atrophy in single leg-immobilized iNOS knockout (KO) and wild-type (WT) mice. The left leg was immobilized for 1 wk, and the right leg was used as the control. Muscle weight and contraction-stimulated glucose uptake were reduced by immobilization in WT mice, which was accompanied with increased iNOS expression in skeletal muscle. Deficiency of iNOS attenuated muscle weight loss and the reduction in contraction-stimulated glucose uptake by immobilization. Phosphorylation of Akt, mTOR, and p70S6K was reduced to a similar extent by immobilization in both WT and iNOS KO mice. Immobilization decreased FoxO1 phosphorylation and increased mRNA and protein levels of MuRF1 and atrogin-1 in WT mice, which were attenuated in iNOS KO mice. Aconitase and superoxide dismutase activities were reduced by immobilization in WT mice, and deficiency of iNOS normalized these enzyme activities. Increased nitrotyrosine and carbonylated protein levels by immobilization in WT mice were reversed in iNOS KO mice. Phosphorylation of ERK and p38 was increased by immobilization in WT mice, which was reduced in iNOS KO mice. Immobilization-induced muscle atrophy was also attenuated by an iNOS-specific inhibitor N(6)-(1-iminoethyl)-l-lysine, and this finding was accompanied by increased FoxO1 phosphorylation and reduced MuRF1 and atrogin-1 levels. These results suggest that deficiency of iNOS attenuates immobilization-induced skeletal muscle atrophy through reduced oxidative stress, and iNOS-induced oxidative stress may be required for immobilization-induced skeletal muscle atrophy.     

Modulating effect of opioid peptides on hemopoiesis in stress

The influence of leu-enkephalin and dalargin on the blood system was studied during immobilization stress in mice. The early transmitted reactions of the peripheral blood were shown to decrease upon single drug infusions after immobilization. At later terms the activation of bone marrow hematopoiesis was not registered in mice receiving opioid peptides in contrast to the control animals. It correlates with drug-induced decrease in the mitotic activity of bone-marrow cells. Suppressive effect of opioids on hematopoiesis during stress was connected with their decreasing effect on corticosteroid level in the animal plasma. The latter can suggest indirect influence of enkephalins on bone marrow hematopoiesis in immobilization stress.     

Quantitation of changes in gene expression of norepinephrine biosynthetic enzymes in rat stellate ganglia induced by stress

Enzymes involved in catecholamine synthesis are present in the highest concentration in the adrenal medulla, however they were found also in other, mainly nervous tissues. The aim of our study was to quantify the exact concentration of tyrosine hydroxylase (TH) and dopamine-ss-hydroxylase (DBH) mRNA in rat stellate ganglia under control conditions and at different intervals after exposure to immobilization stress (IMO). In rats immobilized once for 2h, we determined TH and DBH mRNA in different time intervals up to 22 h after the end of the stress stimulus. TH immunoreactive protein levels were also determined in stellate ganglia. TH and DBH mRNA levels were quantified by RT-competitive-PCR.In stellate ganglia, the concentration of TH mRNA was 17+/-1.6 amol/microg of total RNA, which is approximately 30-times lower than in the adrenal medulla. The concentration of DBH mRNA in the stellate ganglia was 2601+/-203 amol/microg of total RNA, which is the concentration similar to adrenal medulla, but is 150-times higher than concentration of TH mRNA in stellate ganglia. After a single 2-h immobilization the highest elevation of TH and DBH mRNA levels was measured 22 h after the termination of the stress stimulus. Repeated immobilization (7 days, 2h daily) did not produce further increase in TH and DBH mRNA levels compared to already elevated levels in adapted control group (immobilized for 6 days, 2h daily and decapitated 22 h later). Levels of TH protein were significantly changed only after the repeated immobilization.This study compared for the first time the precise amounts of TH and DBH mRNA in rat stellate ganglia under control conditions and after immobilization stress, and indicates large differences in their concentration. TH and DBH mRNA concentrations in stellate ganglia are markedly elevated for a prolonged period of time after termination of the stress stimuli.