首页|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

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

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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.
Impacts of Yantiao Decoction on Intestinal Barrier Injury in Rats with Acute Pancreatitis by Regulating the RhoA/ROCK Signaling Pathway
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(TNF-α),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,ROCK 1 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 dam-age to pancreatic and ileal tissues in the high-dose Yantiao Decoction+LPA group increased,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).Conclusion:Yantiao Decoction may improve the inflammatory response and intestinal barrier damage in AP rats by inhibiting the RhoA/ROCK signaling pathway.

Acute pancreatitisYantiao DecoctionRas homolog gene family memberA/Rho kinase signaling pathwayIntestinal barrierInflammationRats

韩丹、王倩、陈天阳、蔡静雯、郑佳萍、徐童、尹成伟

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上海中医药大学附属曙光医院,上海 201203

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

上海市卫生健康委科研项目上海市科委科研项目上海市申康医院发展中心临床科技创新项目

20204Y047320Y21900300SHDC22021211

2024

中国中医急症
中华中医药学会

中国中医急症

CSTPCD
影响因子:1.144
ISSN:1004-745X
年,卷(期):2024.33(3)
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