枳实通降颗粒通过干预MK2磷酸化抑制炎症反应防治术后炎性肠梗阻相关性肺损伤  

Zhishi Tongjiang Granule mediated control of MK2 phosphorylation in inhibiting postoperative ileus responsible for lung injury

作　　者：莫黎[1] 李倩[2] 王华帅 李莹[2] 黄丽[2] 何永恒 MO Li;LI Qian;WANG Hua-shuai;LI Ying;HUANG Li;HE Yong-heng(The Second Hospital Affiliated to Hunan University of Chinese Medicine,Changsha 410005,China;Hunan University of Chinese Medicine,Changsha,410208,China;The Hospital Affiliated to Hunan Academy of Traditional Chinese Medicine,Changsha 410006,China)

机构地区：[1]湖南中医药大学第二附属医院,湖南长沙410005 [2]湖南中医药大学,湖南长沙410208 [3]湖南省中医药研究院附属医院,湖南长沙410006

出　　处：《中成药》2021年第8期2041-2047,共7页Chinese Traditional Patent Medicine

基　　金：湖南省中医药管理局重点研究室⁃中医药防治肛肠疾病重点研究室项目(湘中医药函[2020]51);长沙市自然科学基金项目(kq2014217);湖南中医药大学中医学国内一流建设学科开放基金(2018ZYX18);湖南中医药大学研究生科研创新课题(2018CX17)。

摘　　要：目的研究枳实通降颗粒对P38通路中MK2磷酸化及术后炎性肠梗阻(POI)相关性肺损伤的影响,探讨其作用机制。方法先将84只大鼠随机分为空白组,假手术组,模型组,枳实通降颗粒低、中、高剂量组(4.2、8.3、16.6 g/kg)和普芦卡必利组(0.18 mg/kg)。造模术后6 h,所有大鼠均按5 mL/kg给药量一次性灌胃给药。药物干预组予相应药物,其余各组予同等量生理盐水。术后24 h取材,检测各组大鼠肺组织中炎症因子IL⁃6、IL⁃8、TNF⁃α水平的变化及髓过氧化酶(MPO)的活性改变,HE染色观察肺组织的病理形态学改变、Western⁃blot及PCR分别检测肺组织中MK2/p⁃MK2蛋白及mRNA的表达情况,并检测支气管肺泡灌洗液(BALF)中炎症细胞的数量。结果与空白组和假手术组比较,模型组大鼠肺组织的病理评分及炎症因子IL⁃6、IL⁃8、TNF⁃α水平、支气管肺泡灌洗液(BALF)中肺泡中性粒细胞、巨噬细胞及淋巴细胞计数、p⁃MK2蛋白及mRNA的表达水平、MPO的活性均明显偏高(P<0.01)。与模型组比较,枳实通降颗粒中、高剂量组大鼠肺组织病理评分较低(P<0.01);而药物干预各组肺组织中炎症因子IL⁃6、IL⁃8、TNF⁃α水平、支气管肺泡灌洗液(BALF)中肺泡中性粒细胞、巨噬细胞及淋巴细胞计数、p⁃MK2蛋白及mRNA的表达水平、MPO的活性均明显低予模型组(P<0.01),以枳实通降颗粒中、高剂量组效果最明显。但各组大鼠肺组织中MK2蛋白及mRNA表达均无明显差异。结论枳实通降颗粒能有效的抑制炎症反应防治POI相关性肺损伤的发生,干预MK2的磷酰化进而抑制炎症发生是其主要的作用机制之一。AIM To study the effects of Zhishi Tongjiang Granule on the phosphorylation of MK2 in p38 pathway and the lung injury associated with postoperative ileus(POI).METHODS Eighty⁃four rats were randomly divided into blank group,sham operation group,model group,Zhishi Tongjiang Granule groups for low⁃dose,medium⁃dose and high⁃dose uses(4.2,8.3,16.6 g/kg),and prucapride group(0.18 mg/kg).At 6 hours after modeling,all rats were given the corresponding drug(5 mL/kg)or same volume of normal saline by gavage.Twenty⁃four hours after the operation,the lung tissue of the rats were subjected to the detection of the levels of inflammatory factors IL⁃6,IL⁃8,TNF⁃αand the activity of myeloperoxidase(MPO);the observation of the pathological changes by HE staining;and the detections of protein and mRNA expression of MK2 and p⁃MK2 by Western blot and PCR,and the number of inflammatory cells in bronchoalveolar lavage fluid(BALF)as well.RESULTS Compared with the blank group and the sham operation group,the model group displayed significantly increased numbers of alveolar neutrophils,macrophages and lymphocytes in BALF,higher pathological score and levels of inflammatory factors IL⁃6,IL⁃8 and TNF⁃α,level of p⁃MK2 protein and mRNA expression,and MPO activity(P<0.01).When comparing with the model group,we observed lower pathological scores in medium⁃dose and high⁃dose Zhishi Tongjiang Granule groups(P<0.01);significantly lower levels of inflammatory factors IL⁃6,IL⁃8,TNF⁃α,less number of alveolar neutrophils,macrophages and lymphocytes in BALF,reduced level of p⁃MK2 protein and mRNA expression,and activity of MPO in all groups intervened with drugs(P<0.01).And among all the groups,the groups intervened with medium⁃dose and high⁃dose Zhishi Tongjiang Granule took a lead.However,we found no significant difference in the expression of MK2 protein and mRNA among the groups.CONCLUSION Zhishi Tongjiang Granule have their role in control of MK2 phosphorylation as a mechanism contributing to the effecti

关 键 词：术后炎性肠梗阻 大鼠 炎症反应 MK2 枳实通降颗粒 肺损伤 

分 类 号：R285.5􀆰[医药卫生—中药学]