马钱苷对脓毒症大鼠炎症反应及肠道屏障损伤的影响  

Effects of loganin on inflammatory response and intestinal barrier damage in septic rats

作　　者：王灿 李岩涛[1,2] 周正 王璐鹏 高媛媛 范少希[2,6] WANG Can;LI Yantao;ZHOU Zheng;WANG Lupeng;GAO Yuanyuan;FAN Shaoxi(Dept.of Critical Care Medicine,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Clinical Medical College,Hebei University of Chinese Medicine,Shijiazhuang 050011,China;Dept.of Pharmacy,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Dept.of Vascular Surgery,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Dept.of Obstetrics,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China;Dept.of Infection Control,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北省中医院重症医学科,石家庄050011 [2]河北中医药大学临床医学院,石家庄050011 [3]河北省中医院药学部,石家庄050011 [4]河北省中医院血管外科,石家庄050011 [5]河北省中医院产科,石家庄050011 [6]河北省中医院感染控制科,石家庄050011

出　　处：《中国药房》2025年第5期574-578,共5页China Pharmacy

基　　金：河北省中医药类科研计划课题(No.2022065,No.2020103)。

摘　　要：目的探讨马钱苷通过调节Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶1(ROCK1)信号通路对脓毒症大鼠炎症反应及肠道屏障损伤的影响及机制。方法采用盲肠结扎和穿刺法建立脓毒症大鼠模型,并随机分为脓毒症组、马钱苷低剂量组(50 mg/kg马钱苷,灌胃)、马钱苷高剂量组(200 mg/kg马钱苷,灌胃)、阳性对照组(0.2 mg/kg阿托伐他汀,腹腔注射)、马钱苷高剂量+溶血磷脂酸(LPA)组(200 mg/kg马钱苷,灌胃+10 mg/kg RhoA激活剂LPA,腹腔注射),另设假手术组,每组10只,每6 h给药1次,连续给药4次。末次给药24 h后,检测大鼠血清中炎症因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、IL-1β水平;观察大鼠回肠组织病理学变化并进行Chiu’s肠黏膜损伤评分;检测大鼠回肠组织中D-乳酸、D-氨基酸氧化酶(DAO)、内毒素水平,闭锁小带蛋白(ZO-1)、闭锁蛋白(Occludin)阳性染色面积百分比以及RhoA、ROCK1的蛋白相对表达水平。结果与脓毒症组比较,马钱苷低剂量组、马钱苷高剂量组大鼠的ZO-1、Occludin阳性染色面积百分比均显著升高,IL-6、TNF-α、IL-1β、DAO、D-乳酸、内毒素水平和Chiu’s肠黏膜损伤评分以及RhoA、ROCK1蛋白的相对表达水平均显著降低(P<0.05),大鼠回肠组织的破坏程度得到缓解,组织水肿及炎性浸润均明显减轻,且马钱苷高剂量组的改善效果均优于马钱苷低剂量组(P<0.05);与马钱苷高剂量组比较,RhoA激活剂LPA可显著逆转上述指标的变化趋势(P<0.05)。结论马钱苷能减轻脓毒症大鼠炎症反应及肠道屏障损伤,其机制与抑制RhoA/ROCK1信号通路有关。OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic rats by regulating the Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil forming protein kinase 1(ROCK1)signaling pathway.METHODS A sepsis rat model was established by cecal ligation and puncture,and randomly divided into sepsis group,loganin low-dose group(50 mg/kg loganin,gavage),loganin high-dose group(200 mg/kg loganin,gavage),positive control group(0.2 mg/kg atorvastatin,intraperitoneal injection),and loganin high-dose+lysophosphatidic acid(LPA)group(200 mg/kg loganin gavage and intraperitoneal injection of 10 mg/kg RohA activator LPA).An additional sham surgery group was established.Each group consisted of 10 rats,and medications were administered once every 6 hours for 4 times.After 24 hours of the last intervention,the levels of serum inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and IL-1βwere detected.The pathological changes of ileal tissue were observed and Chiu’s intestinal mucosal injury score was also performed.The levels of intestinal function-lactate dehydrogenase(D-lactate),D-amino acid oxidase(DAO)and endotoxin,the percentages of zonula occludens-1 protein(ZO-1)and Occludin positive staining area,as well as protein expressions of RhoA,and ROCK1 were all detected.RESULTS Compared with the sepsis group,the percentages of ZO-1 and Occludin positive areas increased significantly in loganin low-dose and high-dose groups;while the levels of IL-6,TNF-α,IL-1β,DAO,D-lactate and endotoxin,Chiu’s intestinal mucosal injury score as well as protein expressions of RhoA and ROCK1 decreased significantly(P<0.05);the destruction of rat ileal tissue was alleviated,and tissue edema and inflammatory infiltration were significantly reduced;moreover,the improvement effect in loganin high-dose group was superior to that in loganin low-dose group(P<0.05).Compared with loganin high-dose group,RhoA activator LPA reversed the trend of changes in the above indic

关 键 词：马钱苷 脓毒症 RhoA/ROCK1信号通路 炎症反应 肠道屏障损伤 

分 类 号：R965[医药卫生—药理学]