枳实及其有效成分柚皮苷预防术后肠粘连的作用机制分析  

Investigation of Mechanism of Aurantii Fructus Immaturus and Naringin in Preventing Postoperative Intestinal Adhesion

作　　者：樊玉青 张婷兰 刘艳[2] 陈畅[2] 陈莎[2] 姜金铸 程锦堂[2] 刘安[2] 郭丛[2] 闫智勇[1] FAN Yuqing;ZHANG Tinglan;LIU Yan;CHEN Chang;CHEN Sha;JIANG Jinzhu;CHENG Jintang;LIU An;GUO Cong;YAN Zhiyong(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]西南交通大学生命科学与工程学院,成都610031 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2022年第24期50-57,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2019YFC1906601)。

摘　　要：目的:研究枳实及柚皮苷对大鼠术后肠粘连的预防作用并探究其作用机制。方法:采用大鼠盲肠刮擦模型研究枳实和柚皮苷对肠粘连的预防作用,雄性SD大鼠造模后随机分为模型组、地塞米松磷酸钠组及枳实低、中、高剂量组(1.58、3.15、6.30 g·kg^(-1)·d^(-1)),另设假手术组仅进行开腹处理,给药7 d后用Nair法评估肠粘连情况,采用苏木素-伊红(HE)染色观察盲肠组织病理形态,免疫组化检测盲肠粘连组织中基质金属蛋白酶-9(MMP-9)的表达;同时,雄性SD大鼠造模后随机分为模型组、地塞米松磷酸钠组及柚皮苷低、中、高剂量组(50、100、200 mg·kg^(-1)·d^(-1)),另设假手术组仅进行开腹处理。给药7 d后评估肠粘连情况,采用HE染色观察盲肠组织病理形态,免疫组化检测盲肠粘连组织中MMP-9的表达,蛋白质免疫印迹法分析盲肠组织中转化生长因子-β_(1)(TGF-β_(1))和α-平滑肌肌动蛋白(α-SMA)的表达。结果:枳实能抑制大鼠术后肠粘连的形成,组织病理学结果显示,其能减少受损盲肠组织中的炎性细胞浸润,并呈剂量依赖性地上调黏附组织中MMP-9的表达;柚皮苷各剂量组均能明显抑制大鼠术后肠粘连,减少组织中炎性细胞浸润和纤维增生,呈剂量依赖性地上调黏附组织中MMP-9的表达,并能抑制盲肠组织中TGF-β_(1)和α-SMA的表达。结论:枳实及其有效成分柚皮苷均能有效预防术后肠粘连,其作用可能与减轻组织纤维化和加速细胞外基质降解有关。Objective:To investigate the preventive effect and mechanism of Aurantii Fructus Immaturus and naringin on postoperative intestinal adhesion in rats.Method:The preventive effect of Auranti Fructus Immaturus and naringin on intestinal adhesion was studied by cecal scraping model of rats,the mode rats were randomly divided into model group,dexamethasone sodium phosphate group and Aurantii Fructus Immaturus low,medium and high dose groups(1.58,3.15,6.30 g·kg^(-1)·d^(-1)),tsham-operated group was treated with an incision in the abdomen.Adhesion was assessed by Nair method after 7 d of administration.Hematoxylineosin(HE)staining was used to observe the pathological morphology and inflammatory cell infiltration of cecum,the expression of matrix metalloproteinase-9(MMP-9)in cecal adhesion was detected by immunohistochemistry.Meanwhile,intestinal adhesion model rats were randomly divided into model group,dexamethasone sodium phosphate group,naringin low,medium,high dose groups(50,100,200 mg·kg^(-1)·d^(-1)),and the sham-operated group was treated with an incision in the abdomen.Adhesion was assessed after 7 d of administration,HE staining was used to observe the pathological morphology and inflammatory cell infiltration in the cecum,and the expression of MMP-9 in the cecal adhesion tissue was detected by immunohistochemistry.Expressions of transforming growth factor-β_(1)(TGF-β_(1))and α-smooth muscle actin(α-SMA)in cecum were analyzed by western blot.Result:Aurantii Fructus Immaturus could inhibit the formation of postoperative intestinal adhesions in rats,reduce the inflammatory response of damaged cecum tissue,and up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner.All dose groups of naringin could significantly inhibit the formation of postoperative intestinal adhesions in rats,reduce inflammatory cell infiltration and fibrous proliferation in tissue,up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner,and inhibit the expression of TGF-β_(1) a

关 键 词：枳实 柚皮苷 肠粘连 纤维化 基质金属蛋白酶-9(MMP-9) 转化生长因子(TGF) α-平滑肌肌动蛋白(α-SMA) 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] R96R574.4