The preventive effect of Huoxue Jiangtang Decoction on pancreatic β cell apoptosis and its influence on scrib protein expression in type 2 diabetes rats
LIU Deliang1 LI Huilin1 QU Xin1 ZHAO Hengxia1 CHU Shufang1 LIU Xuemei1 ZENG Lin2 ZHANG Xuewen2
1.Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, Guangdong Province, Shenzhen 518033, China;
2.the Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangdong Province, Shenzhen 518033, China;
3.Institute of Traditional Chinese Medicine Master, Shaanxi University of Chinese Medicine, Shaanxi Province, Xianyang 712046, China
Abstract:Objective To investigate the preventive effect of Huoxue Jiangtang Decoction on pancreatic β cell apoptosis and its influence on scrib protein expression in type 2 diabetes mellitus rats. Methods The type 2 diabetes mellitus model was induced by high fat and high calorie diet and intravenous injection of low dose of Streptozotocin. By SPSS software, all model rats were divided into model group, herbal group, Metformin group, besides, normal group was added, 10 rats in each group. After treatment, the blood glucose, insulin and lipids were tested; the pancreatic β cell apoptosis was examined by terminal-deoxynucleoitidyl transferase mediated nick end labeling method; and scrib protein expression was detected by Western blot in extracted and purified pancreatic islet cells. Results Compared with model group, the levels of fasting blood-glucose, 2 h postprandial blood glucose, fasting insulin, 2 h postprandial insulin, insulin resistance index and total cholesterol, triacylglycerol, low density lipoprotein cholesterin in herbal group and Metformin group were all decreased, the differences were statistically significant (P < 0.05 or P < 0.01), while high density lipoprotein cholesterol had no obvious changes, the difference was not statistically significant (P > 0.05). Compared with model group, the β cell apoptosis indices in herbal group and Metformin group were also decreased (P < 0.01), meanwhile, the scrib protein expression in islet cells was increased significantly (P < 0.01). Conclusion Huoxue Jiangtang Decoction treatment has the effects of regulating blood lipid, decreasing blood glucose, improving insulin resistance, which can effectively prevent β cell apoptosis. The mechanism may be related to the upregulation of scrib protein expression in islet cells.
刘德亮1 李惠林1 渠昕1 赵恒侠1 楚淑芳1 刘雪梅1 曾霖2 张学文3. 活血降糖饮对2型糖尿病大鼠胰岛β细胞凋亡的防治作用及对scrib蛋白表达的影响[J]. 中国医药导报, 2018, 15(33): 4-7,12.
LIU Deliang1 LI Huilin1 QU Xin1 ZHAO Hengxia1 CHU Shufang1 LIU Xuemei1 ZENG Lin2 ZHANG Xuewen2. The preventive effect of Huoxue Jiangtang Decoction on pancreatic β cell apoptosis and its influence on scrib protein expression in type 2 diabetes rats. 中国医药导报, 2018, 15(33): 4-7,12.
[1] Wang Z,Adair LS,Cai J,et al. Diet Quality Is Linked to Insulin Resistance among Adults in China [J]. J Nutr,2017, 147(11):2102-2108.
[2] Luo B,Zhang J,Hu Z,et al. Diabetes-related behaviours among elderly people with pre-diabetes in rural communities of Hunan,China:a cross-sectional study [J]. BMJ Open,2018,8(1):e15747.
[3] Chen C,Wu S,Lin X,et al. ERK5 plays an essential role in gestational beta-cell proliferation [J]. Cell Prolif,2017, 51(3):e12410.
[4] Dlamini Z,Mokoena F,Hull R. Abnormalities in alternative splicing in diabetes:therapeutic targets [J]. J Mol Endocrinol,2017,59(2):R93-R107.
[5] Pearson HB,Mcglinn E,Phesse TJ,et al. The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis [J]. Mol Cancer,2015,14:169.
[6] Perez E,Lindblad JL,Bergmann A. Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS,macrophages and JNK in Drosophila [J]. Elife,2017,6:e26747.
[7] 刘德亮.血瘀和脂毒与糖脂代谢紊乱的关系及活血降糖饮的治疗作用[D].广州:广州中医药大学,2015.
[8] Gotoh M,Maki T,Satomi S,et al. Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic ductal or portal venous collagenase injection [J]. Transplantation,1987,43(5):725-730.
[9] 李惠林,张志玲,李顺民,等.活血降糖方对Ⅱ型糖尿病人红细胞膜脂区流动性的影响[J].陕西中医学院学报,2000,23(4):44-45.
[10] 张志玲,李惠林,董彦敏,等.活血降糖饮对2型糖尿病代谢及血液流变学的疗效观察[J].中国中医基础医学杂志,2004,10(7):70-71.
[11] Bajaj M,Suraamornkul S,Kashyap S,et al. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes [J]. J Clin Endocrinol Metab,2004,89(9):4649-4655.
[12] Litwak SA,Wali JA,Pappas EG,et al. Lipotoxic Stress Induces Pancreatic beta-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System [J]. J Diabetes Res,2015,2015:280615.
[13] Lupi R,Dotta F,Marselli L,et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets:evidence that beta-cell death is caspase mediated,partially dependent on ceramide pathway,and Bcl-2 regulated [J]. Diabetes,2002,51(5):1437-1442.
[14] Huang J,Wu S,Barrera J,et al. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie,the Drosophila Homolog of YAP [J]. Cell,2005,122(3):421-434.
[15] Yeung B,Khanal P,Mehta V,et al. Identification of Cdk1-LATS-Pin1 as a novel signaling axis in anti-tubulin drug response of cancer cells [J]. Mol Cancer Res,2018, 16(6):1035-1045.
[16] Gao Y,Yi J,Zhang K,et al. Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in eso-phageal squamous cell carcinoma [J]. J Exp Clin Cancer Res,2017,36(1):161.
[17] Li H,He F,Zhao X,et al. YAP Inhibits the Apoptosis and Migration of Human Rectal Cancer Cells via Suppression of JNK-Drp1-Mitochondrial Fission-HtrA2/Omi Pathways [J]. Cell Physiol Biochem,2017,44(5):2073-2089.
[18] Andrade D,Mehta M,Griffith J,et al. YAP1 inhibition radiosensitizes triple negative breast cancer cells by targeting the DNA damage response and cell survival pathways [J]. Oncotarget,2017,8(58):98495-98508.
[19] Humbert P,Russell S,Richardson H. Dlg,Scribble and Lgl in cell polarity,cell proliferation and cancer [J]. Bioessays,2003,25(6):542-553.
[20] 刘红媛,马南希,马瑞,等.Roux-en-Y胃旁路术对2型糖尿病大鼠肝及外周胰岛素敏感性的影响[J].中国实验动物学报,2017,25(3):270-274.
[21] Doggett K,Grusche FA,Richardson HE,et al. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling [J]. BMC Dev Biol,2011,11:57.
[22] 上官若男,朱斌,尚画雨,等.改善Ⅱ型糖尿病大鼠糖代谢运动模型的建立[J].中国实验动物学报,2017,25(3):275-280.
[23] Skouloudaki K,Puetz M,Simons M,et al. Scribble participates in Hippo signaling and is required for normal zebrafish pronephros development [J]. Proc Natl Acad Sci USA,2009,106(21):8579-8584.