活血通降方对反流性食管炎模型大鼠食管动力、血清炎症因子及食管下括约肌SCF/c-kit信号通路的影响  

Effects of Huoxue Tongjiang Decoction(活血通降方)on Esophageal Motility,Serum Inflammatory Factors and Lower Esophageal Sphincter SCF/c-kit Signaling Pathway Reflux Esophagitis Model Rats

作　　者：刘琰 唐艳萍[2] 刘磊 李培彩[2] 刘茜 刘思雨 郝旭雯[2] 杨磊[2] LIU Yan;TANG Yanping;LIU Lei;LI Peicai;LIU Xi;LIU Siyu;HAO Xuwen;YANG Lei(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin,301617;Tianjin Nankai Hospital)

机构地区：[1]天津中医药大学研究生院,天津市301617 [2]天津市南开医院

出　　处：《中医杂志》2022年第3期269-275,共7页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82074213,81573737)。

摘　　要：目的探讨活血通降方治疗反流性食管炎的可能作用机制。方法将60只大鼠随机分为空白组、模型组及活血通降方低、高剂量组,每组15只。除空白组外,其余各组均采用改良部分贲门肌切开术+外置幽门部分结扎术制备反流性食管炎模型大鼠。造模成功后当天开始给药,活血通降方低、高剂量组给药量分别为3.68、7.35 g/(kg·d),空白组和模型组给予生理盐水5 ml灌胃,均连续14天。检测食管下括约肌平均肌张力变化率和平均振幅变化率、胃重量及胃排空率。HE染色观察大鼠食管组织病理形态学变化,并进行食管黏膜病理评分;测定血清中炎症因子白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)浓度;免疫荧光法测定Cajal间质细胞(ICCs)数量;免疫印记法检测食管下括约肌中酪氨酸激酶受体(c-kit)、干细胞因子(SCF)、亮氨酸拉链和不育-α基序激酶(ZAK)和磷酸化细胞外信号调节激酶(p-ERK)表达。结果与空白组比较,模型组食管下括约肌平均肌张力变化率和平均振幅变化率、胃排空率、ICCs阳性细胞数、c-kit和SCF表达均降低,胃重量、食管黏膜损伤病理评分、IL-8和TNF-α浓度、ZAK和p-ERK表达均升高(P<0.05或P<0.01)。与模型组相比,活血通降方高剂量组食管下括约肌平均肌张力变化率和平均振幅变化率升高(P<0.01),活血通降方低、高剂量组胃排空率、ICCs阳性细胞数、c-kit和SCF表达均升高,胃重量、食管黏膜病理评分、IL-8和TNF-α浓度、ZAK和p-ERK表达均降低(P<0.05或P<0.01)。活血通降方高剂量组食管下括约肌平均肌张力变化率、平均振幅变化率、ICCs阳性细胞数均高于活血通降方低剂量组(P<0.05或P<0.01)。结论活血通降方可能通过降低食管下括约肌中ZAK表达,抑制p-ERK表达,一方面激活SCF/c-kit信号通路,促进食管及胃动力;另一方面降低血清中IL-8和TNF-α浓度改善食管下括约肌黏膜炎症,从而治疗反流性�Objective To explore the possible mechanism of Huoxue Tongjiang Decoction(活血通降方,HTD)in the treatment of reflux esophagitis(RE).Methods Sixty rats were randomly divided into blank group,model group,low dose HTD group(L-HTD)and high dose HTD group(H-HTD)group,with 15 rats in each group.Except for the blank group,the rats were given modified partial cardia myotomy and external partial partial pylorus ligation to develop the model of RE.HTD with a dose of 3.68 g(/kg·d)and 7.35 g(/kg·d)were administered in the L-HTD and H-HTD group,respectively,while 5 ml normal saline was given by gavage to both the blank group and the model group since the day when the model was successfully developed.All the administrations lasted for 14 consecutive days.The change rate of the average muscle tone and the average amplitudes of lower esophageal sphincter(LES),the stomach weight and the gastric emptying rate were measured.HE staining was used to observe the histopathologi⁃cal changes of the esophagus tissue,and the pathological score of esophageal mucosa was evaluated.The concentra⁃tions of the inflammatory factor interleukin 8(IL-8)and tumor necrosis factorα(TNF-α)in serum were measured.The number of interstitial cells of Cajal(ICCs)was detected by immunofluorescence,and the expressions of tyrosine kinase receptor(c-kit),stem cell factor(SCF),leucine zipper and sterile alpha motif containing kinase(ZAK)and phosphorylated extracellular signal regulated kinase(p-ERK)in the LES were detected by western blotting.Re⁃sults Compared to those in the control group,the change rates of the average muscle tone and the average ampli⁃tudes of LES,the gastric emptying rate,the number of ICCs-positive cells,and the expression of c-kit and SCF in the model group decreased,while the stomach weight,the pathological score of the esophageal mucosa,the concentration of IL-8 and TNF-α,and the expressions of ZAK and p-ERK increased(P<0.05 or P<0.01)in the model group.Compared to those in the model group,the change rates of the average

关 键 词：反流性食管炎 活血通降方 食管下括约肌 SCF/c-kit信号通路 炎症因子 食管动力 CAJAL间质细胞 

分 类 号：R285.5[医药卫生—中药学]