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目的探讨参附注射液(SFI)对大鼠重症急性胰腺炎(SAP)及其肝损伤的保护作用和可能机制。方法42只雄性Wistar大鼠随机分为3组。SAP组(n=18),采用逆行十二指肠胰胆管注射50%牛磺胆酸钠溶液制备SAP模型;SAP+SFI组(n=18),建模前2 h给予SFI 10 mL/kg(体质量)预处理。假手术(SO)组(n=6)。建模成功后3,6,12 h,分别取下腔静脉血液、胰腺和肝脏组织,并记录腹水量。光镜下观察肝胰病理改变;全自动生化分析仪检测血液淀粉酶和ALT水平;半定量RT-PCR检测肝脏组织中肿瘤坏死因子TNF-αmRNA的表达;SP免疫组化法检测肝脏组织中核转录因子-κB(NF-κB)活性。结果SAP组肝胰病理改变严重程度、腹水量、血清淀粉酶和ALT水平随时间推移不断升高,显著高于SO组(P<0.01);肝脏TNF-αmRNA表达明显升高,术后6 h最显著,均显著高于SO组(P<0.01或P<0.05);肝脏NF-κB活性明显增强,术后3h最显著,均显著高于SO组(P<0.01或P<0.05)。与SAP组相比,SAP+SFI组各时点肝胰病理改变程度、腹水量均显著降低(P<0.01或P<0.05),血液淀粉酶和ALT水平显著降低(P<0.01或P<0.05),肝脏TNF-αmRNA表达显著减少(P<0.01或P<0.05),NF-κB活性显著降低(P<0.01或P<0.05)。结论SFI对大鼠SAP具有防护作用,并能减轻其肝损伤。保护肝脏的机制可能与抑制NF-κB活化进而下调炎性细胞因子TNF-αmRNA表达水平有关。
Objective To investigate the protective effect and possible mechanism of Shenfu injection (SFI) on severe acute pancreatitis (SAP) and liver injury in rats. Methods Forty-two male Wistar rats were randomly divided into 3 groups. In SAP group (n=18), 50% sodium taurocholate solution was injected into the retrograde duodenal pancreatic duct to prepare SAP model; SAP+SFI group (n=18) was given SFI 10 mL/kg 2 h before modeling. (Body weight) pretreatment. Sham (SO) group (n=6). 3, 6, and 12 h after successful modeling, the vena cava blood, pancreas and liver tissues were removed and the amount of ascites was recorded. The histopathological changes of hepatopancreas were observed under light microscope; the levels of blood amylase and ALT were detected by automatic biochemical analyzer; the expression of tumor necrosis factor-α mRNA was detected by semi-quantitative RT-PCR; the nuclear transcription was detected by SP immunohistochemical method. Factor-κB (NF-κB) activity. Results The severity of hepatic pancreatic pathological changes, ascites volume, serum amylase and ALT levels in SAP group increased with time, which was significantly higher than that of SO group (P<0.01). The expression of TNF-α mRNA in liver was significantly increased at 6 h postoperatively. The most significant were significantly higher than the SO group (P<0.01 or P<0.05). The activity of NF-κB in the liver was significantly increased, and the most significant 3 h after operation was significantly higher than that of the SO group (P<0.01 or P<0.05). Compared with SAP group, the pathological changes of hepatic pancreas and the amount of ascites were significantly lower in SAP+SFI group at each time point (P<0.01 or P<0.05), and blood amylase and ALT levels were significantly lower (P<0.01 or P<0.05). ), The liver TNF-α mRNA expression was significantly reduced (P <0.01 or P <0.05), NF-κB activity was significantly reduced (P <0.01 or P <0.05). Conclusion SFI has protective effect on rat SAP and can reduce liver damage. The mechanism of liver protection may be related to the inhibition of NF-κB activation and the down-regulation of inflammatory cytokine TNF-α mRNA expression levels.