酸枣仁皂苷A通过抑制核因子-κB通路减轻小鼠脓毒症所致肝损伤实验研究

Jujuboside A alleviates sepsis-induced liver injury via inhibiting activation of NF-κB pathway in mice

目的:探究酸枣仁皂苷A对小鼠脓毒症所致肝损伤的保护作用,并分析可能机制。方法:将48只小鼠随机平均分为四组,每组12只。对照组腹腔注射0.9%氯化钠溶液;脓毒症组在腹腔注射脂多糖建立脓毒症模型;低剂量组在脓毒症模型中腹腔注射10 mg/kg酸枣仁皂苷A;高剂量组在脓毒症模型中腹腔注射40 mg/kg酸枣仁皂苷A。观察各组小鼠存活率。采用HE染色观察肝损伤情况,比较各组肝损伤评分。利用原位末端转移酶标记(TUNEL)技术观察肝细胞凋亡情况。检测各组小鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,以及血清和肝组织肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)。采用免疫印迹技术检测核因子-κB(NF-κB)通路p-p65和IκB蛋白表达。结果:酸枣仁皂苷A能够提高脓毒症小鼠的存活率。与对照组比较,脓毒症组肝组织细胞凋亡率增加,ALT、AST、TNF-α和IL-6水平升高,p-p65蛋白表达增加,IκB蛋白表达降低均(均P<0.05)。与脓毒症组比较,低剂量组和高剂量组肝组织细胞凋亡率减少,ALT、AST、TNF-α和IL-6水平降低,p-p65蛋白表达降低,IκB蛋白表达增加,且呈剂量依赖性(均P<0.05)。结论:酸枣仁皂苷A可能通过抑制NF-κB通路减轻小鼠脓毒症引起的肝损伤。

Objective:To investigate the protective effect of Jujuboside A on sepsis-induced liver injury in mice,and to analyze the possible mechanism.Methods:Forty-eight mice were randomly divided into four groups,12 mice in each group.The control group was intraperitoneally injected with 0.9%sodium chloride solution.The sepsis model was established by intraperitoneal injection of LPS in the sepsis group.In the low-dose group,10 mg/kg Jujuboside A was injected intraperitoneally in the sepsis model.In the high-dose group,40 mg/kg Jujuboside A was injected intraperitoneally in the sepsis model.The survival rate of mice in each group was observed.HE staining was used to observe liver injury,and the liver injury scores of each group were compared.Hepatocyte apoptosis was observed by TUNEL.The levels of serum ALT,AST,TNF-αand IL-6 in serum and liver tissue were detected.Western blot was used to detect p-p65 and IκB protein expression in NF-κB pathway.Results:Jujuboside A could improve the survival rate of septic mice.Compared with the control group,the apoptosis rate of liver tissue,the levels of ALT,AST,TNF-αand IL-6,the expression of p-p65 protein were increased,and the expression of IκB protein was decreased in the sepsis group(all P<0.05).Compared with the sepsis group,the apoptosis rate of liver tissue,the levels of ALT,AST,TNF-αand IL-6,the expression of p-p65 protein were decreased,and the expression of IκB protein was increased in the low-dose group and the high-dose group in a dose-dependent manner(all P<0.05).Conclusion:Jujuboside A may alleviate sepsis-induced liver injury via inhibiting activation of NF-κB pathway in mice.