| 1 | mTOR/HIF-1α信号通路在布-加综合征肝纤维化中的作用机制研究显示文摘目的探讨mTOR/HIF-1α信号通路在布-加综合征(B-CS)肝纤维化中的作用机制。方法雄性C57小鼠20只按随机数字表法分为假手术(Sham)组、假手术+雷帕霉素(Sham+Ra)组、B-CS组、B-CS+雷帕霉素(B-CS+Ra)组,每组均5只。于肝后段下腔静脉(IVC)部分结扎构建B-CS小鼠模型;Sham组未结扎IVC。Sham+Ra和B-CS+Ra组小鼠隔天腹腔注射雷帕霉素(2 mg/kg,5%DMSO溶液配制),Sham组和B-CS组注射同等剂量5%DMSO溶液。6周后取材,部分肝脏组织用于制作石蜡切片进行苏木精-伊红、天狼星红染色观察病理变化,免疫组织化学染色检测肝组织中α-SMA、Fibrinogen的表达;新鲜肝脏组织提取蛋白和RNA,分别用Western-blot检测α-SMA、Fibrinogen、p-mTOR、mTOR、HIF-1α、CollagenⅠ、VEGF蛋白水平,实时荧光定量PCR检测mTOR、HIF-1α、VEGF mRNA水平。计量资料用均数±标准差(±s)表示,组间的比较采用单因素ANOVA检验。结果病理染色结果显示,B-CS组小鼠肝脏中央静脉周围及肝窦淤血严重,窦间隙增宽,胶原沉积增加,表明本研究成功建立小鼠B-CS肝纤维化模型。Sham组纤维化指标α-SMA、CollagenⅠ蛋白,mTOR通路相关指标p-mTOR、HIF-1α蛋白,微血栓指标Fibrinogen蛋白表达量分别为0.027±0.012、0.337±0.008、0.138±0.024、0.296±0.113、0.733±0.192;B-CS组分别为0.986±0.001、0.927±0.055、0.936±0.044、1.693±0.443、1.612±0.068,两组相比差异有统计学意义(P<0.05)。B-CS+Ra组表达量分别为0.707±0.078、0.311±0.024、0.332±0.094、0.254±0.117、0.569±0.075,与B-CS组相比,差异具有统计学意义(P<0.05)。结论 mTOR/HIF-1α信号通路在小鼠B-CS肝纤维化中被显著激活,该通路可通过调节微血栓形成,参与肝纤维化发展。 | 张跃辉 李素新 杨净 李丁洋 李林 王培举 党晓卫 | 2022 | 国际外科学杂志2022，49，4： | 0 |
| 2 | Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157,L-NAME and L-arginine in rats显示文摘BACKGROUND After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats,there is failed vasculature,and finally,increased adhesion formation.We hypothesized that unlike nitric oxide(NO)-agents,L-NAME and/or L-arginine,the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects(“vascular recruitment”)means attenuated bowel adhesion formation and NO-and malondialdehyde(MDA)-tissue values.AIM To focused on the bowel adhesion and the therapy with the BPC 157,its most and application of NO-agents.METHODS Along with defect creation,medication was(1)during surgery,once,at 1 min after defect creation as an abdominal bath(1 mL/rat),BPC 157(10μg/kg,10 ng/kg,1 mL/rat),an equivolume of saline,L-NAME(5 mg/kg),L-arginine(200 mg/kg)alone and/or combined.Alternatively,medication was(2)intraperitoneally once daily,first application at 30 min after surgery,last application 24 h before assessment at d 7 or d 14.As a postponed therapy to preexisting adhesion(3),BPC 157(10μg/kg,10 ng/kg intraperitoneally,1 mL/rat)was given once daily since d 7.RESULTSThe recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect,which occurs rapidly.Lastly,also applied as post-treatment,BPC 157 creates attenuated adhesions,minimal or no adhesion.Contrarily,NO-agents have diverse initial and final effects:The initial weakening of blood vessel disappearance and finally,severe worsening of adhesions(LNAME)vs the initial weakening of blood vessel disappearance and finally,attenuation of adhesions formation(L-arginine),which counteract each other response given together.Importantly,BPC 157 maintains its beneficial effect also when given with NO-agents(L-NAME+BC 157;L-arginine+BPC 157;L-NAME+L-arginine+BPC 157).Finally,with respect to the increased NO-and MDAvalues-adhesion tissue formation relation,unlike diverse effect of the NO-agents,the BPC 157 application effect regularly combines decrease on the increased NOand MDA-values and the beneficial outcome(less adhesion formation).CONCLUSION BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation. | Lidija Berkopic Cesar Slaven Gojkovic Ivan Krezic Dominik Malekinusic Helena Zizek Lovorka Batelja Vuletic Andreja Petrovic Katarina Horvat Pavlov Domagoj Drmic Antonio Kokot Josipa Vlainic Sven Seiwerth Predrag Sikiric | 2020 | World Journal of Gastrointestinal Pharmacology and Therapeutics2020，11，5： | 0 |
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