黄芩甙对重症急性胰腺炎大鼠胰腺转化生长因子β1表达的影响

Effect of baicalin on the expression of transforming growth factor β1 in the pancreas of rats with severe acute pancreatitis

目的观察黄芩甙对重症急性胰腺炎（SAP）大鼠胰腺组织转化生长因子β1（TGF-β1）表达的影响。方法将45只大鼠随机分为假手术组、模型组、黄芩甙组,每组15只。假手术组打开腹腔后仅翻动胰腺和十二指肠后关腹,其余两组采用逆行胰胆管注射3.5%牛黄胆酸钠法制造SAP模型。造模后10min,黄芩甙组经股静脉给予5%黄芩甙,其余两组给予等量生理盐水。给药3,6,12h,测定血清淀粉酶,胰腺组织髓过氧化物酶（MPO）和肿瘤坏死因子-α（TNF-α）的含量,免疫组化法和RT-PCR法检测胰腺组织TGF-β1的表达,用积分光密度（IOD）评价免疫组化切片TGF-β1的表达结果。结果①假手术组大鼠胰腺组织结构完整,模型组胰腺及周围有皂化斑的形成,胰腺水肿、出血、炎细胞浸润,胰腺组织结构破坏明显,有大片坏死区;黄芩甙组较模型组病理改变显著改善。②给药后各时间点,模型组及黄芩甙组血清淀粉酶水平显著高于假手术组（P〈0.05）,黄芩甙组血清淀粉酶水平较模型组显著降低（P〈0.05）;③给药后各时间点,模型组和黄芩甙组胰腺组织中MPO,TNF-α含量较假手术组均显著增高（P〈0.05）,黄芩甙组胰腺组织MPO,TNF-α含量较模型组均显著降低（P〈0.05）;④给药后各时间点,假手术组均未见到TGF-β1表达,模型组和治疗组均可见到TGF-β1表达。模型组及黄芩甙IOD显著高于假手术组（P〈0.05）,黄芩甙组IOD较模型组显著降低（P〈0.05）。给药后各时间点,对照组均未见到TGF-β1mRNA表达,模型组TGF-β1mRNA表达随时间延长而增多,黄芩甙组TGF-β1mRNA表达各时间点均低于模型组。结论黄芩甙可能通过下调TGF-β1的表达,抑制TGF-β信号通路介导的炎症反应,减轻胰腺组织损害。

Objective To observe the effect of baicalin on the expression of transforming growth factor β1（TGF-β1）in the pancreas of rats with severe acute pancreatitis（SAP）.Methods Forty-five SD male rats were randomly divided into sham operation group（n=15）,model group（n=15）and baicalin group（n=15）.The abdomen of rats in sham operation group were only opened and sutured,while in the other two groups,the abdomen of rats were opened,and then 3.5% sodium taurocholate was conversely injected to biliopancreatic duct to establish the SAP models.Ten minutes after operation,rats in baicalin group were given 5% baicalin via thigh vein,while rats in the other two groups were injected with equal volume of saline.At 3,6 and 12 h after administration,the level of serum amylase was examined,the contents of MPO and TNF-α in pancreas were determined,the expression of TGF-β1 was examined by immunohistochemical analysis and RT-PCR,and positive immunohistochemical result was analyzed with integral optical density（IOD）.Results ①There was no obvious structural changes in rat pancreas in sham operation group,but edema,bleeding and saponified spots in pancreas were found in model group.However,pathological changes in baicalin group were significantly improved compared with model group.②At 3,6 and 12 h after administration,the serum amylase levels in model group and baicalin group were significantly higher than those in sham operation group（P〈0.05）,and the serum amylase level in baicalin group was significantly lower than that in model group（P〈0.05）.③At 3,6 and 12 h after administration,the contents of MPO and TNF-α in rat pancreatic tissues were significantly higher in model group and baicalin group than those in sham operation group（P〈0.05）,while they were significantly lower in baicalin group than those in model group（P〈0.05）.④There was no positive expression of TGF-β1 in rat pancreas in sham operation group at different time points.However,positive expression of TGF-β1 was observed in the rat pancreas in model group and baicalin group.The values of IOD in model group and baicalin group were significantly higher than that in sham operation group（P〈0.05）,and the value of baicalin group was significantly higher than that in model group（P〈0.05）.There was no TGF-β1 mRNA expression in pancreas in sham operation group at different time points.The degree of TGF-β1 mRNA expression in baicalin group was lower than that in model group at different time points.Conclusion By reducing the expression of TGF-β1,baicalin could suppress TGF-β signaling pathway and reduce the pancreas inflammatory damage.