卡巴胆碱对多器官功能障碍综合征小鼠脏器功能和结构的保护作用

目的:观察卡巴胆碱(carbachol,Car)对酵母多糖致多器官功能障碍综合征(MODS)小鼠多脏器功能和结构损伤的防护作用。方法:采用腹腔注射酵母多糖的方法复制小鼠MODS模型。雄性C57BL/6小鼠随机分为正常对照组(n=10),MODS 6、24、48 h组(n=30)和MODS Car 6、24、48 h防治组(n=30)。MODS组在致伤后腹腔注入生理盐水;MODS Car防治组在致伤前24 h内分3次灌胃注入卡巴胆碱。观察酵母多糖致伤后早期(48h内)动物死亡率,检测各组血丙氨酸转氨酶活性、尿素氮和肌酐水平,镜下观察致伤后48 h动物肝、肺、肾、心等脏器的组织病理学改变。结果:在酵母多糖致伤后48h内,MODS组小鼠死亡率达26.6%,MODS Car防治组的小鼠死亡率为10.0%。MODS组小鼠血浆ALT、BUN和Cr在伤后6h升高,而同时间点经卡巴胆碱预处理的小鼠血浆ALT、BUN和Cr仅略有升高,明显低于MODS组。光镜下观察发现,MODS组小鼠肝脏、肺脏、肾脏和心脏发生明显的病理改变,主要表现为脏器实质细胞浊肿、变性,间质充血、水肿和炎性细胞浸润,而卡巴胆碱防治组小鼠上述病变明显减轻。结论:预防性给予卡巴胆碱可以降低MODS急性期动物的死亡率,减轻脏器功能和结构的损伤,对急性炎症期的脏器损伤具有保护作用。

Protective effect of carbachol on organ function and structure in mice with multiple organ dysfunction syndrome

Objective:To observe the protective effect of carbachol (Car) on organ function and structure in mice with multiple organ dysfunction syndrome(MODS).Methods:MODS model of mice was replicated by intraperito- neal injection of zymosan.Male C57BL/6 mice were randomly divided into normal control(n=10),MODS 6,24, 48 hours(n=30),and MODS Car 6,24,48 hours groups(n=30).MODS mice were injected with normal saline after intraperitoneal injection of zymosan.Mice of MODS Car group received carbachol by gavage 3 times per day prior to injection of zymosan.The mortality rate was recorded,plasma alanine aminotransforase activity (ALT) and renal function parameters were determined,and pathological changes in liver,lung,kidney and heart were observed.Results:During 48 hours after the injection of zymosan,the mortality rate in MODS Car mice was 10.0%,which was lower than that of MODS mice (26.6%).Plasma ALT activity,blood urea nitrogen (BUN) and creatinine (Cr) concentrations in MODS mice increased compared with those in normal controls,but the above parameters tended to approach normal range in MODS Car group.Marked pathological changes were noted in liver,lungs,kidney and heart of MODS mice,including degeneration of parenchyma cells,hyperaemia and edema of interstitial tissue,and inflammatory cells infiltration.There were mild pathological changes in differ- ent tissues of mice treated with carbachol.Conclusion:Preventive administration of carbachol might reduce the mortality rate and abate organ dysfunction and structure damage in mice at early phase of MODS.