Objective To study the changes of expressions of intestinal mucosal tight junction proteins ZO-1 and Occludin in rats with acute intrahepatic cholestasis,and explore its mechanisms.Methods Forty SD rats aged 21 days were randomly divided into control group(n=10) and model group(n=30).A single dose(50 mg.kg-1) of α-naphthylisothiocyanate was administered by gavage to each experimental rats to induce acute intrahepatic cholestasis in model group.Rats in control group only administered with caster oil by gavage.At 24 hours,48 hours and 72 hours after gavage,immunohistochemistry and Western blot techniques were used to examine the distribution and expression of tight junction proteins(ZO-1,Occludin),and the results of Western blot were quantitatively analyzed by image analytical system.Results ZO-1 and Occludin were localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells.Compared with control group,the positive stainings of ZO-1 and Occludin in model group at 24 hours after gavage were decreased,the decrease was most obviously at 48 hours,and partly recovered at 72 hours.Western blot demonstrated consistent and significant reduction with immunohistochemistry.The expressions of ZO-1 and Occludin in model group were 0.129 4±0.048 1 and 0.195 0±0.044 1 at 24 hours,0.039 5±0.009 5 and 0.013 7±0.009 2 at 48 hours,0.202 4±0.049 8 and 0.149 4±0.035 5 at 72 hours,which were significantly lower than those in control group(ZO-1:0.288 7±0.023 7,Occludin:0.426 6±0.067 0)(Pa0.01).Conclusions Acute intrahepatic cholestasis induces the abnormal distribution of tight junction proteins and the alteration of their quantity,which affects the intestinal barrier integrity,resulting in impaired barrier function.

Objective To study the effects of live combination bifidobacterium,lactobacillus and enterococcus(BIFICO) on intestinal mucosal epithelium tight junction protein ZO-1 and Occludin in rats with cholestasis.Method Male SD rats of 3 weeks old were randomly divided into control group,model group and BIFICO group.Before making the animal model,BIFICO[4.2×107 viable bacterium counts/(kg·d)] were administered to the rats in BIFICO group for 4 days. The model and control groups were fed by normal saline.At the 5th day after administration,after fasting for 12 h,the model group and BIFICO group were intragastrically administered ANIT(50 mg/kg) for modeling.At 24 h,48 h and 72 h after modeling,every 10 rats in each group were executed for taking terminal ileum tissue.Immunohistochemistry and Western blot techniques were used to examine the distribution and expression of tight junction proteins(ZO-1,Occludin).And the results of Western blot were quantitatively analysed by image analytical system.Result ZO-1 and Occludin were localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells.The positive stainings of ZO-1 and Occludin of model group at 24 h after modeling,were decreased than those of control group;the decrease was most obvious at 48 h,and partly recovered at 72 h.Western blot demonstrated significant reduction consistent with immunohistochemistry.The protein expressions in model group were(ZO-1 0.1294±0.0481),(Occludin 0.1950±0.0441)at 24 h,(ZO-1 0.0395±0.0095),(Occludin 0.0137±0.0092)at 48 h,(ZO-1 0.2024±0.0498) and(Occludin 0.1494±0.0355)at 72 h respectively,which were significantly lower than those in control group(ZO-1 0.2887±0.0237),(Occludin 0.4266±0.0670)(P0.01);The protein expressions in BIFICO group were(ZO-1 0.2110±0.0367),(Occludin 0.3056±0.0572)at 24 h,(ZO-1 0.1173±0.0423),(Occludin 0.0521±0.0123)at 48 h,(ZO-1 0.2601±0.0191),(Occludin 0.2050±0.0721)at 72 h,which have statistical difference compared to those in model group at both time point(P0.05).Conclusion Probiotics supplement can be effective in acute cholestasis by improving the intestinal barrier function.

1906年由诺贝尔奖获得者俄国著名微生物教授梅奇尼柯夫(Metchnikoff)首先提出"肠道菌有益论",1965年Lilly和Stillwell首先使用益生菌剂(probiotics)一词以来,各国科学家围绕益生剂定义进行深入研究和讨论,直到2001年10月由世界卫生组织和联合国粮食与农业组织(WHO/FAO)召集有关益生剂专家对益生剂进行了定义:益生剂是指摄入一定数量,对宿主健康产生有益作用的活的微生态制剂.这个定义强调了益生剂必须是活的微生态制剂,必须是摄入足够剂量,应用后且对宿主健康产生有益作用.

This paper demonstrate that cortical neurons in dissociated cultures exhibited synchronized spontaneous Ca2+ spikes.The synchronized spontaneous Ca2+ spikes are synaptically driven,as it is blocked by tetrodotoxin,and by the glutamate receptor antagonist CNQX/APV.The oscillatory activity is not influenced by GABAA receptor antagonist picrotoxin,suggesting that they entirely rely on glutamatergic neurotransmission.We have also found that these Ca2+ spikes are dependent on an influx of extracellular Ca2+ but are independent of mobilization of Ca2+ from intracellular Ca2+ stores.Ca2+ entry occurred primarily through L-type voltage-gated calcium channels,since nifedipine completely blocked these Ca2+ spikes.

Objective To study the anti-tumor effects of TM-TNF-α mimic peptide displayed on phages in vivo. Methods Peptides-presenting phages were prepared and their anti-tumor effects were compared. Then, the peptide with the best effect and the suitable concentration was subcutaneously injected on day 3 after H22 tumor cell challenge. The tumor growth was observed. Results TM-TNF-α mimic peptide displayed on phages can dramatically inhibit the growth of tumor (P0.01) in a dose dependent manner. HE staining showed infiltration of lymphocytes in the tumor tissues, while there was infiltration of neutrophils and plasma cells but not lymphocytes in the tumor tissues treated by s-TNF. Conclusion Direct injection of TM-TNF-α mimic peptide displayed on phages could effectively suppress the tumor growth. The mechanism involved in the tumoricidal activity induced by peptides was different from that of sTNF-α.