苦杏仁苷对肾纤维化大鼠的保护作用及其机制  

Protective Effect and Mechanism of Amygdalin on Renal Fibrosis in Rats

作　　者：李想 刘庆 高晨 周红兵[1] 常虹[1] 王佳 白万富[1] 石松利[1,2] LI Xiang;LIU Qing;GAO Chen;ZHOU Hongbing;CHANG Hong;WANG Jia;BAI Wanfu;SHI Songli(School of Pharmacy,Baotou Medical College,Baotou 014060,China;Institute of Bioactive Substance and Function of Mongolian Medicine and Chinese Materia Medica,Baotou Medical College,Baotou 014060,China)

机构地区：[1]包头医学院药学院,包头014060 [2]包头医学院蒙中药活性物质与功能研究所,包头014060

出　　处：《医药导报》2022年第9期1282-1289,共8页Herald of Medicine

基　　金：国家自然科学基金资助项目(81641137,81760782);内蒙古自然科学基金资助项目(2019MS08189,2020MS08078,2021LHMS08013);内蒙古自治区第十一批“草原英才”人才工程[(2021)8];内蒙古自治区“草原英才工程”青年创新创业人才项目(Q2017046);内蒙古自治区高等学校科学研究项目(NJZY21048);内蒙古自治区卫生健康科技计划项目(202202226);包头医学院博士科研启动基金资助项目(BSJJ201814);包头医学院研究生科研创新项目(bycx2020006,bycx2021009)。

摘　　要：目的探讨蒙古扁桃苦杏仁苷对肾纤维化大鼠的作用及其机制。方法SD雄性大鼠60只,按体质量随机分为6组:假手术组、模型对照组、贝那普利组和苦杏仁苷小、中、大剂量组,每组10只。除假手术组外其余各组大鼠均采用左侧输尿管梗阻方法造模。连续灌胃给药21 d后处死,记录大鼠24 h尿量、计算大鼠肾脏脏器系数;测定大鼠血清中尿素氮(BUN)、肌酐(Scr)、白蛋白(ALB)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量及组织中SOD、MDA、羟脯胺酸(HYP)含量;荧光定量聚合酶链反应(PCR)法检测组织内转化生成因子β_(1)(TGF-β_(1))、Smad3、Smad7 mRNA的表达;采用苏木精-伊红(HE)和马松(Masson)染色观察左侧肾脏组织病理变化。结果与假手术组比较,模型对照组大鼠尿量显著减少(P<0.01),血清和组织SOD活力显著降低(P<0.01),肾脏脏器系数、BUN、Scr、ALB水平及血清和组织MDA含量、组织HYP含量显著升高(P<0.01);TGF-β_(1)、Smad3 mRNA表达量显著升高,Smad7 mRNA表达量显著降低(P<0.01)。与模型对照组比较,苦杏仁苷给药组肾间质及肾小管损伤情况显著改善,纤维化程度显著降低(P<0.01),24 h尿量显著增加(P<0.01),脏器系数显著降低(P<0.01),其中以小剂量组效果最显著;苦杏仁苷小剂量组BUN、Scr、ALB水平、血清和组织MDA含量及HYP含量(P<0.01)均显著降低,血清SOD活力显著升高(P<0.01),TGF-β_(1)、Smad3 mRNA的表达显著下调(P<0.01),Smad7 mRNA的表达(P<0.01)显著上调;苦杏仁苷中剂量组Scr水平、ALB水平、血清和组织MDA含量及HYP含量均显著降低(P<0.01),组织SOD活力显著升高(P<0.01);苦杏仁苷大剂量组血清和组织MDA含量均显著降低(P<0.01)。结论苦杏仁苷对肾纤维化大鼠肾脏具有良好的保护作用,能提高机体抗氧化能力,以小剂量作用效果最好,其作用机制可能是干预TGF-β_(1)/Smad信号通路。Objective To investigate the effect and its possible mechanism of amygdalin(AMY)on renal fibrosis rats.Methods A total of 60 male SD rats were randomly divided into sham operated group(SDG),model control group(MOD),benazepril hydrochloride tablets group(BHT),and amygdalin low-,medium-,high-dose groups(AMY-L,AMY-M,AMY-H).Renal fibrosis model was prepared by unilateral ureteral obstruction.After 21 days of continuous intragastric administration,the rats were sacrificed,the 24 h urine output was recorded,and the renal viscera coefficients were calculated;Blood urea nitrogen(BUN),serum creatinine(Scr),albumin(ALB),superoxide dismutase(SOD),malondialdehyde(MDA)in serum and the content of SOD,MDA,and hydroxyproline(HYP)in the tissue were detected.Quantitative polymerase chain reaction(qPCR)method was used to detect transforming growth factorβ_(1)(TGF-β_(1)),Smad3,Smad7 mRNA expression level in the kidney.The hematoxylin-eosin(HE)and Masson staining was used to observe the histopathological changes in the kidney tissue.Results Compared with the SDG,the urine output was significantly reduced(P<0.01),the SOD activity of serum and tissue was significantly reduced(P<0.01),the renal viscera coefficients,the levels of BUN,Scr,ALB,and the MDA content of serum and tissue,and the HYP content of tissue increased significantly(P<0.01)in the MOD group.The expressions levels of TGF-β_(1),Smad3 mRNA in the tissue were significantly increased,and Smad7 mRNA was significantly reduced(P<0.01).Compared with the MOD group,the renal interstitial and renal tubular injury were alleviated significantly,the degree of fibrosis was significantly reduced(P<0.01),24-hour urine output was significantly increased(P<0.01),and renal viscera coefficients were significantly reduced(P<0.01)by the AMY,among which the AMY-L has the most significant effect.The BUN,Scr,ALB levels,MDA content of serum and tissue and HYP content were significantly reduced(P<0.01),SOD activity of serum was significantly increased(P<0.01),and the expressions of TGF-β_(1) and

关 键 词：苦杏仁苷 蒙古扁桃 肾纤维化 TGF-β_(1)/Smad信号通路 

分 类 号：R282.71[医药卫生—中药学] R285[医药卫生—中医学]