孕康口服液对脾虚流产模型小鼠的安胎作用研究  

Anti-miscarriage Effect of Yunkang Oral Liquid on Spleen-deficiency Abortion Model Mice

作　　者：许万枫 陈青青 刘慧芳 苏洁[1] 胡慧明[2] 陈素红[3] 吕圭源[1] XU Wanfeng;CHEN Qingqing;LIU Huifang;SU Jie;HU Huiming;CHEN Suhong;LYU Guiyuan(Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China;Science and Technology College of Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,Jiangxi,China;Zhejiang University of Technology,Hangzhou 310014 Zhejiang,China)

机构地区：[1]浙江中医药大学,浙江杭州310053 [2]江西中医药大学科技学院,江西南昌330004 [3]浙江工业大学,浙江杭州310014

出　　处：《中药新药与临床药理》2020年第5期553-558,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：浙江省重点实验室项目(2012E10002);江西省教育厅科技项目(GJJ161627)。

摘　　要：目的观察孕康口服液对"番泻叶+米非司酮"致脾虚流产模型小鼠的安胎作用。方法将60只ICR孕鼠按妊娠顺序随机分为正常组,模型组,孕康口服液低、中、高剂量组(9、18、36 mL·kg^-1)和黄体酮组(0.038 g·kg^-1);采用灌胃给予1 g·mL^-1番泻叶水煎液0.4 mL联合米非司酮6 mg·kg^-1制备脾虚流产模型小鼠;同时按上述剂量灌胃给药,给药体积0.04 mL·g^-1,连续给药10 d,每天1次,正常组、模型组给予等体积生理盐水。观察小鼠排便(计算稀便率、腹泻率)和胚胎丢失情况(计算胚胎丢失率);计算脾脏、胸腺、卵巢的脏器指数;ELISA法检测血清孕酮(P)、Th1型细胞因子肿瘤坏死因子α(TNF-α)和γ干扰素(INF-γ)、Th2型细胞因子白细胞介素4(IL-4)和白细胞介素10(IL-10)水平;HE染色进行子宫组织病理形态学观察;Western Blot法检测子宫组织中孕激素受体(PR)蛋白的表达情况。结果与正常组比较,模型组小鼠稀便率和胚胎丢失率明显升高(P<0.01),体质量、脾脏、胸腺、卵巢指数明显降低(P<0.05,P<0.01),血清P、IL-4和IL-10水平明显降低(P<0.01),INF-γ/IL-10明显升高(P<0.01),子宫内膜出现蜕膜化不明显、蜕膜组织变性且排列松散、血管数量减少等病变,且子宫组织中PR蛋白表达量明显减少(P<0.01)。与模型组比较,孕康口服液各剂量组均能明显降低稀便率、胚胎丢失率和INF-γ/IL-10水平,明显升高IL-10水平(P<0.05,P<0.01);孕康口服液高、中剂量组能明显升高体质量(P<0.05,P<0.01),明显上调子宫组织中PR蛋白表达(P<0.01);孕康口服液高、低剂量组能明显升高模型小鼠血清P水平(P<0.05,P<0.01),改善子宫病变。结论孕康口服液对脾虚流产模型小鼠具有明显的安胎作用,其作用机制可能是通过调节Th1/Th2细胞因子平衡、升高孕酮水平和上调孕激素受体表达。Objective To observe the effect of Yunkang oral liquid on miscarriage of spleen-deficiency model mice induced by Sennae folium combined with mifepristone.Methods Sixty ICR pregnant rats were randomly divided into six groups:the normal group,the model group,Yunkang oral liquid low,medium and high dose groups(9,18,36 mL·kg^-1)and the progesterone group(0.038 g·kg^-1).Spleen-deficiency abortion model mice was induced by intragastric administration of 1 g·mL^-1 Sennae folium decoction 0.4 mL combined with mifepristone 6 mg·kg^-1,and the dosing volume is 0.04 mL·g^-1,the normal group and the model group were given the same amount of saline once a day for 10 days.The defecation and the loss of mouse embryos were recorded.The visceral indexes of the spleen,thymus,and ovary were calculated.Serum levels of progesterone(P),Th1 type cytokine tumor necrosis factorα(TNF-α)and interferonγ(IFN-γ),Th2 type cytokine interleukin 4(IL-4)and interleukin-10(IL-10)were detected.The morphology of uterus was visualized by HE staining and the expression of progesterone receptor(PR)protein in uterine tissue was detected by Western Blot.Results Compared with the normal group,the loose stools rate and the embryo loss rate of the model group were significantly increased(P<0.01),the body weight,spleen,thymus,and ovarian indexes were significantly decreased(P<0.05,P<0.01),serum P,IL-4,and IL-10 levels were significantly decreased(P<0.01),INF-γ/IL-10 was significantly elevated(P<0.01);the decidualization of the endometrium was not obvious,the decidual tissue was degenerated and loosely arranged,the number of blood vessels was reduced,and the expression of PR protein in uterus was significantly decreased(P<0.01).Compared with the model group,all doses of Yunkang oral liquid can significantly reduce the embryo loss rate,the loose stools rate and serum INF-γ/IL-10 level,and significantly increase serum IL-10 level(P<0.05,P<0.01).High and medium doses of Yunkang oral liquid can significantly increase the body weight(P<0.05,P<0.01),promot

关 键 词：孕康口服液 脾虚流产模型 TH1/TH2细胞因子 孕激素受体 孕酮 小鼠 

分 类 号：R285.5[医药卫生—中药学]