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

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) and α-SMA in cecal tissue.Conclusion:Aurantii Fructus Immaturus and naringin can reduce postoperative intestinal adhesion formation in rat model,and their effects may be related to reducing tissue fibrosis and accelerating extracellular matrix degradation.