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目的观察低分子量肝素(LMWH)对大鼠重症急性胰腺炎(SAP)肝组织热休克蛋白70(HSP70)表达及血清丙氨酸氨基转移酶(ALT)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和IL-8水平的影响,探讨其对SAP肝损伤保护机制。方法将Wistar大鼠随机分为假手术组、模型组、LMWH组,检测术后24 h和72 h肝组织HSP70的表达、血清ALT、TNF-α、IL-6和IL-8水平及胰腺和肝组织形态学变化。结果镜下可见:假手术组胰腺和肝细胞形态正常;模型组胰腺和肝细胞呈片状坏死及大量炎细胞浸润;LMWH组胰腺和肝细胞有少量的炎细胞浸润及点状坏死。24 h与72 h肝HSP 70表达:24 h比72 h多,依次为:假手术组(0.212±0.051,0.207±0.039),模型组(0.371±0.064,0.314±0.048),LMWH组(0.262±0.062,0.232±0.049),LMWH组表达明显下调与模型组比较(P<0.01)。血清ALT、TNF-α、IL-6和IL-8水平72 h比24 h低,LMWH组与模型组比较(P<0.01),进一步分析,肝HSP 70表达与血清ALT、TNF-α、IL-6和IL-8间呈正相关。结论 LMWH通过下调肝组织HSP70表达,降低血清ALT、TNF-α、IL-6和IL-8水平,减轻SAP肝损伤。
Objective To observe the effect of low molecular weight heparin (LMWH) on the expression of heat shock protein 70 (HSP70), serum alanine aminotransferase (ALT) and tumor necrosis factor-α (TNF-α) in rat with severe acute pancreatitis (SAP) , Interleukin-6 (IL-6) and interleukin-8 (IL-8), and to explore their protective mechanisms against SAP liver injury. Methods Wistar rats were randomly divided into sham operation group, model group and LMWH group. The expression of HSP70, serum ALT, TNF-α, IL-6 and IL-8 levels in liver tissue were measured at 24 h and 72 h after operation, Liver histomorphology changes. Results The results showed that the pancreas and hepatocytes were normal in the sham-operation group. The pancreas and hepatocytes in the model group showed necrosis and massive infiltration of inflammatory cells. Pancreas and hepatocytes in the LMWH group had a small amount of inflammatory cell infiltration and punctate necrosis. The expression of HSP70 in 24 h and 72 h was higher than that in 72 h in 24 h and 72 h, respectively: sham group (0.212 ± 0.051,0.207 ± 0.039), model group (0.371 ± 0.064,0.314 ± 0.048), LMWH group (0.262 ± 0.062,0.232 ± 0.049). The expression of LMWH group was significantly down-regulated compared with model group (P <0.01). The levels of ALT, TNF-α, IL-6 and IL-8 in serum were lower than those in 24 h after 72 h, and the expression of hepatic HSP 70 was positively correlated with serum ALT, TNF-α, IL -6 and IL-8 was positively correlated. Conclusion LMWH can reduce the level of ALT, TNF-α, IL-6 and IL-8 in serum and reduce the hepatic injury in SAP by down-regulating the expression of HSP70 in liver tissues.