姜黄素对大鼠肠缺血再灌注后肠黏膜细胞凋亡及GRP78表达的影响

目的 观察姜黄素对大鼠肠缺血再灌注后肠黏膜细胞凋亡及GRP78表达的影响。方法 30只雄性SD大鼠随机分为假手术组、模型组、姜黄素组。采用无创性动脉夹夹闭肠系膜上动脉1 h后实施再灌注来建立肠缺血再灌注模型，姜黄素组在手术前5 d开始每天按200 mg/kg ig给药1次，假手术组仅分离肠系膜上动脉，不夹闭。采用HE染色观察肠黏膜损伤情况并进行病理评分；TUNEl法观察肠黏膜细胞凋亡情况并计算凋亡指数；Western blotting检测再灌注损伤3 h时肠黏膜GRP78及Caspase-12蛋白表达。结果 模型组肠黏膜损伤严重，绒毛上皮成块脱落，固有层破坏、溃疡，腺体破坏严重；姜黄素组肠黏膜绒毛上皮仅部分脱落，腺体排列紊乱，与模型组比较，病理评分显著降低（P<0.05）；模型组肠黏膜隐窝可见大量凋亡阳性细胞；与模型组比较，姜黄素组肠黏膜隐窝上皮细胞凋亡情况明显减轻，凋亡指数显著下降（P<0.05）；与模型组比较，姜黄素组GRP78蛋白表达量显著增加（P<0.05），Caspase-12蛋白表达量显著下降（P<0.05）。结论 姜黄素有可能通过上调GRP78表达，减少内质网应激所致肠黏膜细胞凋亡，来减轻肠黏膜的再灌注损伤，达到保护肠黏膜作用。

Effect of curcumin on intestinal mucosal cell apoptosis and GRP78 expression after intestinal ischemia-reperfusion in rats

Objective To observe the possible effect of curcumin on GRP78 expression and epithelial cells apoptosis in rats after intestinal ischemia reperfusion. Method Thirty male SD rats were randomly divided into three groups: sham group, model group and curcumin group, 10 rats in each group. An experimental model of intestinal ischemia reperfusion in rats was established by the occlusion of superior mesenteric artery for one hours by small atraumatic clip, followed by reperfusing, and sham group were prepared in the same way without the occlusion. Curcumin group were feeded curcumin at a dose of 200 mg/kg per day 5 days before operating. Intestinal tissue injury severity of rat was tested by HE assay. The apoptosis of epithelial cells was measured by TUNEL method. The expression of GRP78 in rats tissue after 3 h reperfusion was detected by Western blotting. Results In the model group, intestinal mucosa was damaged seriously, villous epithelium was exfoliated, lamina propria was damaged, ulcerated and glands were damaged seriously. Compared with the model group, the pathological score of curcumin group decreased significantly (P < 0.05). Compared with the model group, the apoptosis of intestinal mucosal crypt epithelial cells in curcumin group decreased significantly (P < 0.05). Compared with the model group, the expression of GRP78 and caspase-12 in curcumin group increased significantly (P < 0.05). Conclusion Curcumin could reduce intestinal ischemia reperfusion injury in rats by up-regulation GRP78 expression.