姜黄素对顺铂所致胃组织ICC损伤的保护作用及机制

目的:探索顺铂对胃组织Cajal间质细胞(Cajal interstitial cells,ICCs)结构和功能的损伤以及姜黄素的保护作用。方法:选用成年雄性昆明种小鼠,随机分为对照组、顺铂组和顺铂+姜黄素组,每组各10只。姜黄素(200 mg/kg/d)混悬液连续灌胃15天。顺铂于实验结束前5天开始腹腔注射(2 mg/kg/d)共5天。计算每只小鼠最后5天的体重增减值,停药24 h后测量小鼠的胃排空率。电镜检测胃组织ICC超微结构,并测定特异性反映ICC功能变化的Ano1蛋白和m RNA的表达情况。结果:注射顺铂后各组小鼠的体重和胃排空率均显著降低(P0.01);与顺铂组相比,姜黄素预先灌胃组小鼠体重下降较少(P0.01),胃排空率有所回升(P0.05)。注射顺铂后,胃组织中ICCs受损,尤其与周围神经和肌肉间的缝隙连接增大甚至断裂,而姜黄素可以减轻这种损伤。同时,顺铂组胃组织中Ano1 m RNA和蛋白表达均下降(P0.01),加姜黄素组有所改善(P0.05)。结论:而姜黄素可通过减轻顺铂所致胃组织ICC结构损伤以及增强Ano1表达进而增强ICC慢波起博功能。

Protective Effects and Mechanisms of Curcumin on the Damage of Cisplatin to ICC in Gastric Tissue

ABSTRACT Objective: To explore the damage of cisplatin to the structure and function of cajal interstitial cells(ICCs)in gastric tis- sue and the protective effect of curcumin. Methods: Adult kunming male mice were randomly divided into control group(NC), cisplatin group(DDP)and cisplatin+curcumin group(DDP+Cur) with 10 mice in each group. Curcumin(200 mg/kg/d)mixed with the suspension by intragastric administration for a total period of 15 days. Intraperitoneal injection of cisplatin (2 mg/kg/d) was started from the last 5th day, for a total of 5 days. The weight gain and loss of each mouse on the last 5 days were calculated, and the gastric emptying rate of each mouse was measured after stopping the drug for 24 h. The ultrastructure of ICC in gastric tissue was detected by electron microscope and the expression of Ano1 protein and mRNA in gastric tissue, which specifically responded to the changes of ICCs, were detected also. Results: The weight and gastric emptying rate of mice were significantly decreased after injection of cisplatin (P<0.01). Compared with cisplatin group, cisplatin+curcumin group had less weight loss (P<0.01) and gastric emptying rate were significantly increased(P<0.05). After in- jection of cisplatin, ICCs in gastric tissue were damaged, especially the gap junctions between peripheral nerve and muscular cells were winden or even broken, and curcumin could alleviate these damage. In addation, the expression of Ano1mRNA and protein in cisplatin group decreased (P<0.01), while it was improved significantly in cisplatin+curcumin group (P<0.05). Conclusion: Curcumin can reduce cisplatin-induced structural damage of ICC by increasing the expression of Ano1 and incraesing the function of slow waves generation.