紫檀芪对革兰阴性菌致脓毒症模型大鼠肝损伤的改善作用  

Improvement Effect of Pterostilbene on Liver Injury in Sepsis Model Rats Induced by Gram-Negative Bacteria

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作  者:刘建军 曹炜炜 林莫凡 张叶 郭雪梅 LIU Jianjun;CAO Weiwei;LIN Mofan;ZHANG Ye;GUO Xuemei(Fengxian Central Hospital,Shanghai,China 201400;Shanghai Fourth People's Hospital,Shanghai,China 200080)

机构地区:[1]上海市奉贤区中心医院,上海201400 [2]上海市第四人民医院,上海200080

出  处:《中国药业》2025年第8期50-55,共6页China Pharmaceuticals

基  金:上海市虹口区卫生健康委员会中医药课题立项建设项目[HKQ-ZYY-2020-46]。

摘  要:目的探讨紫檀芪对革兰阴性菌致脓毒症模型大鼠肝损伤的改善作用。方法将40只SD大鼠随机分为对照组(等体积生理盐水)、模型组(等体积生理盐水)、PTE组(25 mg/kg)和PTE+EX 527组(25,5 mg/kg),各10只。各组大鼠均腹腔注射109 CFU大肠杆菌以复制革兰阴性菌脓毒症大鼠模型,建模前30 min,各组大鼠腹腔注射相应药物或生理盐水。建模后每6 h监测1次,连续观察24 h。苏木精-伊红(HE)染色,观察大鼠肝组织病理形态变化;采用电生化法检测大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、胆红素(BiL)水平;采用酶联免疫吸附试验(ELISA)法检测大鼠肝组织中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、髓过氧化物酶(MPO)及白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;RT-PCR法和Western blot法检测大鼠肝组织中SIRT1、p-STAT3 mRNA及蛋白的表达水平。结果模型组大鼠肝小叶被破坏,肝细胞水肿变性,且有大量炎性细胞浸润;PTE组肝小叶结构趋于完整,仅有少量肝细胞水肿,且炎性细胞浸润较模型组明显减轻;PTE+EX 527组肝组织损伤程度与模型组相似。与模型组比较,PTE组大鼠血清中AST、ALT、BiL水平及肝组织中MPO、IL-6、TNF-α水平均显著降低,肝组织中SOD、GSH水平及SIRT1、p-STAT3 mRNA和蛋白表达水平显著升高(P<0.05);与PTE组比较,PTE+EX 527组大鼠血清中AST、ALT、BIL水平及肝组织中MPO、IL-6、TNF-α水平均显著升高,肝组织中SOD、GSH水平及SIRT1、p-STAT3 mRNA和蛋白表达水平均显著降低(P<0.05)。结论紫檀芪可改善革兰阴性菌所致脓毒症模型大鼠肝损伤,抑制肝细胞的炎性反应,其作用机制可能与激活SIRT1/STAT3信号通路有关。Objective To investigate the improvement effect of pterostilbene on liver injury in sepsis model rats induced by gram-negative bacteria.Methods A total of 40 SD rats were randomly divided into control group(equal volume of normal saline),model group(equal volume of normal saline),PTE group(25 mg/kg)and PTE+EX 527 group(25,5 mg/kg),with 10 rats in each group.Rats in each group were intraperitoneally injected with 109 CFU of Escherichia coli to replicate the sepsis rat model of Gram-negative bacteria.30 minutes before modeling,rats in each group were intraperitoneally injected with corresponding drugs or normal saline.After modeling,the rats were monitored every 6 hours,with continuous observation for 24 hours.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of liver tissue in rats.The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and bilirubin(BiL)in serum of rats were detected by electrobiochemical method.The levels of superoxide dismutase(SOD),glutathione(GSH),myeloperoxidase(MPO),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in liver tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA and protein expression levels of SIRT1 and p-STAT3 in rat liver tissues were detected by RT-PCR and Western blot.Results In the model group,the hepatic lobules of rats were destroyed,the liver cells were edematous and degenerated,and there were a large number of inflammatory cell infiltration.In the PTE group,the structure of hepatic lobules tended to be complete,with only a small amount of hepatocyte edema,and the infiltration of inflammatory cells was significantly reduced compared with the model group.The degree of liver tissue injury in the PTE+EX 527 group was similar to that in the model group.Compared with the model group,the levels of AST,ALT,BiL in serum and MPO,IL-6,TNF-αin liver tissue of PTE group were significantly decreased,and the levels of SOD,GSH,the mRNA and protein expression of SIRT1,p-STAT3 and in liver tissue were signi

关 键 词:紫檀芪 革兰阴性菌 脓毒症 肝损伤 SIRT1/STAT3信号通路 

分 类 号:R965[医药卫生—药理学] R285[医药卫生—药学]

 

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