丹蛭降糖胶囊对糖尿病性骨质疏松大鼠的治疗作用及机制  

Therapeutic Effect and Mechanism of Danzhi Jiangtang Capsules on Diabetic Osteoporosis in Rats

作　　者：侯保健 胡菊萍 严兆丹 蔡莉 张令晖 HOU Bao-Jian;HU Ju-Ping;YAN Zhao-Dan;CAI Li;ZHANG Ling-Hui(The Third People's Hospital of Hubei Province,Hubei 430030 Wuhan,China)

机构地区：[1]湖北省第三人民医院,湖北武汉430030

出　　处：《广州中医药大学学报》2023年第2期421-427,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：湖北省卫生健康委员会科研计划项目(编号:WJ2019F174)。

摘　　要：【目的】探讨丹蛭降糖胶囊对糖尿病性骨质疏松(DOP)大鼠的治疗作用及机制。【方法】将54只大鼠随机分为假手术组,模型组,中药低、中、高剂量组及吡格列酮组,每组9只。除假手术组外,其余组别大鼠均建立DOP模型,建模过程中感染死亡3只。成功建模1 d后,中药低、中、高剂量组大鼠分别灌胃丹蛭降糖胶囊0.54、1.08、2.16 g·kg^(-1)·d^(-1),吡格列酮组灌胃盐酸吡格列酮10 mg·kg^(-1)·d^(-1),模型组和正常组大鼠灌胃等体积生理盐水,连续8周。给药结束后,检测性激素代谢水平,包括雌二醇(E2)、促卵泡生成素(FSH)、促黄体生成素(LH);检测胰岛功能指标,包括空腹血糖(FPG)、空腹胰岛素(FINS)、稳态模式评估法测定的胰岛素抵抗指数(HOMA-IR)及胰岛素敏感指数(ISI);检测骨代谢指标,包括骨钙素(OC)、血钙(Ca)、血磷(P)和碱性磷酸酶(ALP);苏木素-伊红(HE)染色法观察股骨组织病理形态;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测胰腺组织胰岛β细胞凋亡;Western Blot法检测股骨组织胰岛素样生长因子1受体(IGF-1R)、Wnt1、β-catenin蛋白表达。【结果】与假手术组比较,模型组E2水平降低,FSH、LH水平升高,胰岛功能指标FPG、FINS及HOMA-IR值升高,ISI值降低,骨代谢指标OC及ALP含量升高,胰岛细胞凋亡率升高,股骨组织IGF-1R蛋白表达水平升高,Wnt1、β-catenin蛋白表达水平降低(均P<0.05),HE染色结果显示骨质疏松特征病理表现;与模型组比较,中药低、中、高剂量组及吡格列酮组E2水平升高,FSH、LH水平降低,胰岛功能指标FINS、FPG及HOMA-IR值降低,ISI值升高,骨代谢指标OC及ALP含量降低,胰岛β细胞凋亡率降低,IGF-1R蛋白表达水平降低,Wnt1、β-catenin蛋白表达水平升高(均P<0.05),HE染色结果显示骨组织病理形态明显改善。中药高剂量组上述各指标与吡格列酮组比较,差异均无统计学意义(P>0.05)。【结论】丹�Objective To investigate the therapeutic effect and mechanism of Danzhi Jiangtang Capsules on diabetic osteoporosis(DOP)in rats. Methods Fifty-four rats were randomly divided into the sham-operation group, the model group, the low-, medium-and high-dose groups of Chinese medicine and pioglitazone group,with 9 rats in each group. Except for the sham-operation group,DOP model was established in all groups,and 3 rats died of infection during the modeling process. Day 1 after successful modeling, rats in the Chinese medicine low-,medium-and high-dose groups were gavaged with 0.54,1.08 and 2.16 g·kg^(-1)·d^(-1) of Danzhi Jiangtang Capsules, respectively, while rats in the pioglitazone group were gavaged with 10 mg·kg^(-1)·d^(-1) of pioglitazone hydrochloride. At the end of administration, the metabolic levels of sex hormones were detected,including estradiol(E2), follicle-stimulating hormone(FSH) and luteinizing hormone(LH);islet function indicators were detected,including fasting plasma glucose(FPG),fasting insulin(FINS),homeostasis model assessment-insulin resistance(HOMA-IR)and insulin sensitivity index(ISI);bone metabolism indexes including osteocalcin(OC),serum calcium(Ca),serum phosphorus(P)and alkaline phosphatase(ALP)were detected;hematoxylin and eosin(HE) staining was used to observe the pathological morphology of femur;terminal deoxynucleotide transferase-mediated dUTP Nick end labeling(TUNEL)assay was used to detect pancreatic isletβ-cell apoptosis;the protein expressions of insulin-like growth factor 1 receptor(IGF-1R),Wnt1 and β-catenin in femoral tissue were detected by Western Blot. Results Compared with the sham-operation group,the E2 level was decreased,the FSH and LH levels were increased,the islet function indexes FPG,FINS and HOMA-IR values were increased,the ISI value was decreased,the bone metabolism indexes OC and ALP contents were increased,the islet cell apoptosis rate was increased,and the IGF-1R protein expression level in femoral tissue was increased,and the protein expression levels

关 键 词：丹蛭降糖胶囊 糖尿病性骨质疏松 胰岛功能 性激素代谢 骨代谢 胰岛素样生长因子1受体 WNT1 β-catenin 大鼠 

分 类 号：R285.5[医药卫生—中药学]