炎调方调节RhoA/ROCK信号通路对急性胰腺炎大鼠肠屏障损伤的影响  

Impacts of Yantiao Decoction on Intestinal Barrier Injury in Rats with Acute Pancreatitis by Regulating the RhoA/ROCK Signaling Pathway

作　　者：韩丹[1] 王倩[1] 陈天阳[1] 蔡静雯 郑佳萍 徐童 尹成伟[1] Han Dan;Wang Qian;Chen Tianyang;Cai Jingwen;Zheng Jiaping;Xu Tong;Yin Chengwei(Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201203

出　　处：《中国中医急症》2024年第3期429-433,454,共6页Journal of Emergency in Traditional Chinese Medicine

基　　金：上海市卫健委科研课题(20204Y0473);上海市科学技术委员会科研计划项目(20Y21900300);上海市申康医院发展中心临床科技创新项目(SHDC22021211)。

摘　　要：目的观察炎调方调节Ras同源基因家族成员A(RhoA)/Rho激酶(ROCK)信号通路对急性胰腺炎(AP)大鼠肠屏障损伤的影响。方法将84只大鼠随机分为对照组、模型组、炎调方低剂量组、炎调方高剂量组、乌司他丁组、溶血磷脂酸(LPA)组、炎调方+LPA组,每组12只。除对照组外,其他组构建AP大鼠模型。造模成功后立即进行给药处理,每6小时给药1次,共4次。ELISA法检测大鼠血清中淀粉酶、脂肪酶、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、D-乳酸、二胺氧化酶(DAO)水平;HE染色检测大鼠胰腺组织和回肠组织病理变化;免疫组化染色检测大鼠回肠组织中ZO-1、Occludin蛋白平均光密度;Western blotting检测回肠组织中RhoA、ROCK1、ROCK2蛋白表达。结果与对照组比较,模型组大鼠胰腺组织和回肠组织病理损伤严重,淀粉酶、脂肪酶、TNF-α、IL-6、D-乳酸、DAO水平及RhoA、ROCK1、ROCK2蛋白表达升高,ZO-1、Occludin蛋白平均光密度降低(P<0.05);与模型组比较,炎调方低剂量组、炎调方高剂量组、乌司他丁组大鼠胰腺组织和回肠组织病理损伤减轻,淀粉酶、脂肪酶、TNF-α、IL-6、D-乳酸、DAO水平及RhoA、ROCK1、ROCK2蛋白表达降低,ZO-1、Occludin蛋白平均光密度升高,LPA组对应指标变化趋势与上述相反(P<0.05);与炎调方高剂量组比较,炎调方+LPA组大鼠胰腺组织和回肠组织病理损伤加剧,淀粉酶、脂肪酶、TNF-α、IL-6、D-乳酸、DAO水平及RhoA、ROCK1、ROCK2蛋白表达升高,ZO-1、Occludin蛋白平均光密度降低(P<0.05)。结论炎调方可能通过抑制RhoA/ROCK信号通路改善AP大鼠炎症反应及肠屏障损伤。Objective:To explore the impacts of Yantiao Decoction on intestinal barrier injury in rats with acute pancreatitis(AP)by regulating the Ras homolog gene family member A(RhoA)/Rho kinase(ROCK)signal path⁃way.Methods:The 84 rats were randomly divided into the control group,AP group,low dose Yantiao Decoction;group,high dose Yantiao Decoction group,ulinastatin group,lysophosphatidic acid(LPA)group,and high dose Yan⁃tiao Decoction+LPA group,with 12 rats in each group.Except for the control group,all other groups of rats were used to construct AP rat models.Immediately after successful modeling,medication was administered,once every 6 hours,totaling 4 times.ELISA was applied to detect the levels of amylase,lipase,tumor necrosis factor-α(TNFα),interleukin-6(IL-6),D-lactic acid,and diamine oxidase(DAO)in serum;HE staining was applied to detect pathological changes in rat pancreatic and ileal tissues;immunohistochemical staining was applied to detect the av⁃erage optical densities of ZO-1 and Occlusion proteins in rat ileum tissue;Western blotting was applied to detect the expression of RhoA,ROCK1,and ROCK2 proteins in rat ileum tissue.Results:Compared with the control group,the pathological damage to pancreatic and ileal tissues in the AP group rats was severe,the levels of amy⁃lase,lipase,TNF-α,IL-6,D-lactic acid,DAO,and the expression of RhoA,ROCK1 and ROCK2 proteins in⁃creased,the average optical densities of ZO-1 and Occlusion proteins decreased(P<0.05);compared with the AP group,the pathological damage to pancreatic and ileal tissues in rats in the low-dose Yantiao Decoction group,high-dose Yantiao Decoction group,and ulinastatin group was reduced,the levels of amylase,lipase,TNF-α,IL-6,D-lactic acid,DAO,and the expression of RhoA,ROCK1 and ROCK2 proteins decreased,the average optical den⁃sities of ZO-1 and Occlusion proteins increased,the change trend of corresponding indicators in the LPA group was opposite to the above(P<0.05);compared with the high-dose Yantiao Decoction group,the pathological d

关 键 词：急性胰腺炎 炎调方 Ras同源基因家族成员 A/Rho激酶信号通路 肠屏障 炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]