外源性ghrelin在大鼠重症急性胰腺炎并肾损伤中的作用

The effect of ghrelin administration on the severity of kidney injury in severe acute pancreatitis of rats

目的探讨外源性ghrelin在大鼠SAP肾损伤中的作用及机制。方法 72只Wistar大鼠随机分为假手术组(SO组,n=24)、重症急性胰腺炎模型组(SAP组,n=24)和ghrelin干预组(G组,n=24)。SAP组、G组均用3.5%牛磺胆酸钠(1ml/kg)按胰胆管逆行注射法制成重症急性胰腺炎模型,G组在制模前30min和制模后3h腹腔内注射ghrelin(10nmol/kg),SO组、SAP组于相同时间注射等量生理盐水,各实验组大鼠于制模后6h、12h和24h分批取材。光学显微镜下对胰腺和肾脏组织进行病理学评分,全自动生化仪检测血清淀粉酶,酶联免疫吸附法检测血清IL-6、TNF-α、肌酐。结果 1SAP组6h、12h、24h血清淀粉酶、肌酐、TNF-α、IL-6,胰腺及肾脏病理评分均较同时间点SO组升高,差异有统计学意义(P<0.05);2G组6h、12h、24h血清淀粉酶、肌酐、TNF-α、IL-6,胰腺及肾脏病理评分均较同时间点SAP组下降,差异有统计学意义(P<0.05),但均较同时间点SO组升高,差异有统计学意义(P<0.05)。结论外源性ghrelin通过降低TNF-α、IL-6的水平,减轻炎症反应来减轻SAP的严重程度,同时保护肾脏的生理功能。

Objective To investigate the mechanisms involved in the therapeutic effect of ghrelin administration on the severity of acute kidney injury in severe actue pancreatitis（SAP） of rats. Methods Seventy-two wistar rats were randomly di-vided into shamoperated group （group SO, n=24）, severe acute pancreatitis group （group SAP, n=24） and ghrelin intervention group（group G, n=24）. SAP was induced in rats of group SAP and group G by 3.5%sodium taurocholate injection through pan-creaticobiliary duct. In group G, the rats were injected ghrelin intraperitoneally by 10nmol/kg（0.5h before and 3h after the oper-ation）. In group SAP and SO, the rats were injected the same normal saline intraperitoneally at the same time. The tissue and blood of rats were taken at 6 hours,12h and 24h after operation respectively. The pathologic changes of pancreas and kidney were observed and graded under a optical microscope. The level of serum amylase, creatinine, TNF-α, IL-6 were determined by radio-immunoassay. Results ①In group SAP, the level of serum amylase,creatinine,TNF-α, IL-6,the pathologic scores of the pancreas and kidney were significantly higher than those at the same time in group SO （P〈0.05）;②In group G, the level of serum amylase,creatinine,TNF-α, IL-6, the pathologic scores of the pancreas and kidney were significantly lower than those at the same time in group SAP（P〈0.05）, but still significantly higher than those at the same time in group SO（P〈0.05）. Con-clusion The reduction of TNF-α, IL-6 may be the mechanisms involved in the therapeutic effect of ghrelin administration on severity of kidney injury in SAP.