大承气汤对肠源性脓毒症小鼠的保护作用及机制  

Protective effects and mechanism of Dachengqi decoction on intestinal septic mice

作　　者：钟旋[1] 李袁袁 林荣锋[2,3] 姚韵婕 刘伟琼 罗毅平[1] 凌家俊[2] ZHONG Xuan;LI Yuanyuan;LIN Rongfeng;YAO Yunjie;LIU Weiqiong;LUO Yiping;LING Jiajun(Medical Intensive Care Unit,Guangdong Women and Children Hospital,Guangzhou 511442,China;School of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Dongguan Institute of Guangzhou University of Chinese Medicine,Guangdong Dongguan 523808,China)

机构地区：[1]广东省妇幼保健院成人重症监护室,广州511442 [2]广州中医药大学中药学院,广州510006 [3]东莞广州中医药大学研究院,广东东莞523808

出　　处：《中国药房》2023年第17期2101-2106,共6页China Pharmacy

基　　金：广东省中医药局科研项目(No.20211045);东莞广州中医药大学研究院培育项目(No.2023PY0203)。

摘　　要：目的 研究大承气汤(DCQD)对肠源性脓毒症小鼠的保护作用,并从Toll样受体4/髓分化因子88(TLR4/MyD88)信号通路探讨其可能机制。方法 将SPF级雄性C57BL/6J小鼠分为假手术(Sham)组、假手术+大承气汤高剂量(Sham+DCQD-H)组、模型(CLP)组、大承气汤低剂量(DCQD-L)组、大承气汤高剂量(DCQD-H)组、阳性对照(Positive)组。CLP组、DCQD-L组、DCQD-H组和Positive组小鼠均以盲肠结扎穿刺法建立肠源性脓毒症模型;DCQD-L组和DCQD-H组小鼠在术前3 d和术后7 d每天分别按4、8 g/kg(按生药量计)灌胃给予大承气汤;Positive组在术前2 h腹腔注射乌司他丁1次,术后7 d每天腹腔注射乌司他丁1次,剂量均为50 000 U/kg。Sham组和Sham+DCQD-H组仅暴露盲肠,不做结扎及穿刺;Sham+DCQD-H组在术前3 d和术后7 d每天灌胃给予大承气汤(8 g/kg,按生药量计);Sham组和CLP组每天均灌胃和腹腔注射生理盐水各0.2 mL,连续10 d。术后7 d每天评估小鼠脓毒症严重程度,并评估小鼠7 d生存率;末次给药1 h后,检测小鼠血清和回肠组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;观察小鼠肝、肺、肾、回肠组织的病理学形态变化;检测小鼠回肠组织中TLR4、MyD88 mRNA表达水平。结果 与CLP组比较,DCQD-L组、DCQD-H组小鼠脓毒症评分,血清和回肠组织中TNF-α、IL-6水平(DCQD-L组回肠组织中IL-6除外),肝、肺、肾、回肠组织损伤评分,回肠组织中TLR4、MyD88 mRNA表达水平均显著降低(P<0.05或P<0.01);7 d生存率(DCQD-L组除外)显著升高(P<0.05);小鼠肝细胞组织损伤明显改善,炎症浸润和凋亡减少;肺组织损伤有所缓解,肺泡萎缩、出血、水肿均有不同程度的改善;肾组织损伤改善,肾小管管腔扩张减弱;回肠组织损伤及水肿均有明显改善。结论 大承气汤对肠源性脓毒症模型小鼠具有保护作用,其作用机制可能与抑制全身炎症、减轻多器官损伤以及下调TLR4/MyD88信号通路有关。OBJECTIVE To study the protective effects of Dachengqi decoction(DCQD) on intestinal septic mice,and to explore the possible mechanisms from the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88) signaling pathway.METHODS The SPF male C57BL/6J mice were randomly divided into Sham group,Sham+DCQD-H group,model(CLP) group,DCQD-L group,DCQD-H group and Positive group.The model of intestinal sepsis was established by cecal ligation and puncture in CLP group,DCQD-L group,DCQD-H group and Positive group.Three days before the operation and seven days after the operation,DCQD-L group and DCQD-H group were given DCQD intragastrically at 4,8 g/kg(calculated by crude drug),respectively.Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation(at 50 000U/kg).In Sham group and Sham+DCQD-H group,only cecum of mice was exposed without ligation and puncture.Sham+DCQDH group was given DCQD intragastrically(8 g/kg,calculated by crude drug) 3 days before the operation and 7 days after the operation.Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day,for 10 consecutive days.After the operation,the severity of sepsis was assessed,and the 7 d survival rate of mice was assessed.One hour after the last medication,the levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in serum and ileum of mice were determined;the pathological and morphological changes of mice's liver,lung,kidney and ileum were observed;m RNA expressions of the TLR4 and My D88 in ileum were tested.RESULTS Compared with CLP group,sepsis score,the levels of TNF-α and IL-6 in serum and ileum(except for IL-6 in ileum of DCQD-L group),damage score of the liver,lung,kidney and ileum,m RNA expressions of TLR4 and My D88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group(P<0.05 or P<0.01),while 7 d survival rate(except for DCQD-L group) was increased significantly(P<0.05).The damage to liver tissue in mice was signif

关 键 词：大承气汤 脓毒症 炎症因子 器官损伤 Toll样受体4/髓分化因子88信号通路 

分 类 号：R965[医药卫生—药理学] R285.5[医药卫生—药学]