Ghrelin及GHSR在急性坏死性胰腺炎大鼠胰腺组织的表达

Expression of ghrelin and hormone secretagogue receptor in pancreas of rats with acute necrotizingpancreatitis

目的观察急性坏死性胰腺炎（ANP）大鼠胰腺组织ghrelin以及生长激素促分泌素受体（GHSR）的表达，探讨ghrelin在ANP发病机制中的作用。方法70只大鼠按完全随机法分为ANP组和对照组，每组35只。采用逆行胆胰管注射4％牛磺胆酸钠的方法制备大鼠ANP模型；对照组仅开腹，轻翻动胰腺。术后3、6、12、24、48h处死大鼠，取血测血清淀粉酶，取胰腺行常规病理检查并评分，应用RT-PCR和蛋白质印迹法检测胰腺组织ghrelin、GHSR的mRNA及蛋白表达。结果ANP组大鼠血清淀粉酶浓度从造模后3h开始升高，6h达（8244±2950）U／L，显著高于对照组（P〈0．05）；胰腺病理损伤及评分随时间延长逐渐加重，24h评分为（11．91±1．31）分，显著高于对照组的（3．12±1．60）分。ANP组大鼠胰腺组织ghrelinmRNA和GHSRmRNA表达随时间的延长而逐渐升高，48h达峰值，分别为1．29±0．64和0．94±0．16，均显著高于对照组的0．58±0．05和0．19±0．03（P值均〈0．05）。ANP组大鼠胰腺组织ghrelin和GHSR蛋白的表达在48h时达峰值，分别为3．05±0．48和2．34±0．32，均显著高于对照组的2．18±0．23和1．55±0．10（P值均〈0．05）。结论ANP大鼠胰腺组织ghrelin、GHSR的mRNA及蛋白表达均显著增加日与，且与胰腺病变严重程度有关。

Objective To observe the expression of ghrelin and growth hormone secretagogue receptor （GHSR） in pancreas of rats with acute necrotizing pancreatitis （ANP）, and investigate the role of ghrelin in the pathogenesis of ANP. Methods Seventy SD rats were randomly divided into ANP group （ n = 35 ） and control group （n = 35）. ANP model was induced by retrograde injection of 4% sodium taurocholate into the biliary and pancreatic duct. Rats in the control group underwent laparotomy with gentle pancreas manipulation only. At 3, 6, 12, 24, 48 h after ANP induction, the rats were sacrificed, and the serum level of amylase was determined, pathological changes in pancreatic tissue were routinely observed and scored. The expressions of ghrelin mRNA, protein and GHSR mRNA, protein in pancreas were evaluated by RT-PCR and Western blot. Results Serum amylase level began to increase at 3h after sodium taurocholate injection and reached the peak value at 6 h [ （8244 ± 2950） U/L ], which was significantly higher than that in control group （ P 〈 0. 05 ）. Pancreatic injuries was aggravated with time, the pathologic score at 24 h was （11.91 ± 1.31 ） score, which was significantly higher than （3.12 ± 1.60） score in the control group. The expressions of ghrelin mRNA and GHSR mRNA in pancreas of ANP group were increased gradually with time, and were significantly higher thanthose of control group at all time points, at 48 h, 1.29± 0.64 vs0. 58± 0. 05 and 0.94 ± 0.16vs 0. 19 ± 0.03, P 〈 0.05. The expressions of ghrelin protein and GHSR protein in pancreas of ANP group were significantly higher than that in control group at 12, 24, 48 h. at 48 h, 3.05 ±0.48 vs 2.18±0.23 and 2.34±0.32 vs 1.55 ＋ 0. 10 （P 〈 0.05）. Conclusions The expressions of ghrelin mRNA, protein and GHSR mRNA, protein of pancreas are significantly increased in rats of ANP, and are associated with the severity of ANP.