脓毒症大鼠肝损伤机制及参附注射液治疗作用研究

目的:通过大白鼠肠穿孔建立脓毒血症模型,观察大白鼠肝组织中核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α),并使用参附注射液治疗,探讨大白鼠脓毒血症引起肝损伤的发病机制和参附注射液的治疗作用。方法:手术造成大白鼠肠穿孔并引发脓毒血症。健康大白鼠65只,随机分为正常对照组(NS组)、实验组(CLP组)和治疗组(SF组)。NS组开腹,分离出盲肠,穿线不结扎-穿孔,然后关腹,术后腹腔注射生理盐水(20mL/kg)。CLP组开腹,分离出盲肠,结扎并穿孔,然后关腹,术后腹腔注射生理盐水(20mL/kg),然后关腹。SF组术后腹腔注射参附,然后关腹,并每隔10h追加一次给药。根据不同时间点将CLP组和SF组分为3h、6h、12h、24h四个亚组,每个亚组各5只大鼠,在4个不同手术时间点分别通过腹主动脉取血,并无菌提取肝组织标本,检测单个核细胞中NF-κB活性、TNF-α水平。结果:与NS组对比,CLP组:①单个核细胞中NF-κB活性明显增高,6h最明显(P<0.01);②血清TNF-α浓度明显升高,6h最明显(P<0.01);SF组与CLP组对比,参附注射液可显著降低NF-κB活性、TNF-α水平(P<0.01)。结论:①NF-κB和TNF-α参加了脓毒血症的发生发展,导致肝脏损伤;②参附注射液可能通过减少NF-κB以及TNF-α的释放,减轻肝脏损伤,对脓毒血症起治疗作用。

Study on Protective Effect and Mechanism of Shenfu Injection on Liver Injury in Sepsis Rats

Objective:To Study on Protective Effect and Mechanism of Shenfu injection on liver injury in the model of sepsis rats by cecal ligation and puncture(CLP).Methods:Sixty-five Wistar rats were randomLy divided into 3 groups,normal group(NS),experiment group(CLP) and treatment group(SF).The rats of NS group were not subjected to caecum to ligation,and the other treatments were same as those in CLP group.Sepsis rat model was induced by ligating and puncturing caecum,and then the abdomen was closed.Finaly,those rats were injected normal saline(NS)20mL/kg.The rats of SF group were administrated intraperitoneal with 0.5mL/ kg Shenfu injection and 19.5 mL/kg NS after CLP.According to time after CLP,the NS group,CLP group and SF group were divided into,3h,6h,12h and 24h subgroup.Each subgroup had 5 rats.We detected the level of nuclear factor of kappa B(NF-κB),tumor necrosis factor-α(TNF-α) in the model of sepsis rats.Results:In CLP group,compared with NS group: The level of NF-κB and TNF-α was increased and peaked at 6h after CLP(P<0.01)..Compared with CLP group,the level of NF-κB,TNF-α,ALT in SF group was decreased at all observed time(P<0.01).Conclusion:1.NF-κB,TNF-α,which could cause hypotension,liver injury,were involved in the development of sepsis.2.The protective effect of SF might be relevant to its decreasing activation of NF-κB and the release of TNF-α in sepsis rats.