Protective effects of Curcumin analogue L6H4 on kidney from type 2 diabetic rats

doi:10.12047/j.cjap.5448.2017.003

Abstract

Abstract: Objective: To investigate the protective effect of curcumin analogue L6H4 on the kidney from the type 2 diabetic rats.Methods: Twenty-four SPF male SD rats were randomly divided into 3 groups(n=8):normal control group(NC),diabetes mellitus group(DM) and DM+L6H4-treatment group(DT). After rats were fed with high-fat diet for 4 weeks, both the DM and DT groups were injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus models. The rats in DT group were given L6H4 by gavage at the dose of 0.2 mg/kg·d for 8 weeks. After the treatment, the 24 h urinary protein, fasting blood glucose (FBG), triglyceride (TG), serum creatinine(Scr),blood urea nitrogen (BUN) and uric acid (UA) were detected biochemically. The pathological changes of the kidneys were observed under light and transmission electron microscopes. The expressions of TGF-β1, FN and Col IV were detected by immunohistochemistry.Results: The levels of the 24 h urinary protein, FBG, TG, Scr and BUN were elevated significantly in diabetic group(P<0.01). The glomerular volume of DM group rats became irregularly enlarged, diffused mesangial matrix accumulated, with basal membrane proliferous hypertrophy and fusion phenomenon of foot process, the expressions of TGF-β1,FN and Col-IV were elevated significantly (P<0.05). After treated with L6H4, the levels of the 24 h urinary protein, FBG, TG, Scr and BUN were decreased in DT group compared to DM group (P<0.01), the morphological changes of kidney were ameliorated. The expression levels of TGF-β1, FN and Col-IV were downregulated (P<0.05).Conclusion: L6H4 exerts the protective effect on kidneys of type 2 diabetic rats by reducing expression of TGF-β1, inhibiting secretion of Col-IV and FN, relieving the deposition of the extracellular matrix.

Key words: curcumin analogue L6H4, type 2 diabetes, kidney, transforming growth factor-beta 1, rat

LIU Xi, MA Jun, HU Mao-tong, DONG Xi-dan, XIANG Lan-ting, GU Qian-ru, DU Zhuan-yun, CHEN San-mei, CHEN Guo-rong. Protective effects of Curcumin analogue L6H4 on kidney from type 2 diabetic rats[J]. CJAP, 2017, 33(1): 11-15.

References

[1] Gooch JL, Barnes JL, Garcia S, et al. Calcineurin is activated in diabetes and is required for glomerular hypertrophy and ECM accumulation[J]. Am J Physiol Renal Physiol, 2003, 284(1):F144-154.
[2] Chen S, Hong SW, Iglesias-dela Cruz MC, et al. The key role of the transforming growth factor-β system in the pathogenesis of diabetic nephropathy[J]. Ren Fail, 2001, 23(3-4):471-481.
[3] 曾聪聪, 刘曦, 刘网网, 等. 姜黄素衍生物 B06 对 2 型糖尿病大鼠肾脏的保护作用[J]. 中国应用生理学杂志, 2015, 31(1):38-42.
[4] 应丽丽, 倪瑾瑶, 李慧敏, 等. 姜黄素类似物 L6H4 对 2 型糖尿病大鼠心肌的保护作用[J]. 中国病理生理杂志, 2016, 32(1):27-32.
[5] 陈涵斌, 马骏, 李慧敏, 等. 邻苯二甲酸酯染毒哺乳期母鼠对雄性仔鼠睾丸Leydig细胞形态及功能的影响[J]. 中国应用生理学杂志, 2015, 31(2):97-101.
[6] 李旭升, 陈国荣, 李剑敏, 等. 银杏叶提取物对糖尿病大鼠心肌损伤的防护作用. 中国应用生理学杂志, 2005, 21(2):176-178.
[7] Schaan BDA, Lacchini S, Bertoluci MC, et al. Increased renal GLUT1 abundance and urinary TGF-β1 in streptozotocin-induced diabetic rats:implications for the development of nephropathy complicating diabetes[J]. Horm Metab Res, 2001, 33(11):664-669.
[8] 吕佳璇, 李月红. 糖尿病肾病的研究进展[J]. 临床内科杂志, 2016, 33(5):296-299.
[9] Houlihan CA, Akdeniz A, Tsalamandris C, et al. Urinary transforming growth factor-β excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate effects of angiotensin receptor blockade and sodium restriction[J]. Diabetes Care, 2002, 25(6):1072-1077.
[10] Wang JJ, Zhang SX, Mott R, et al. Salutary effect of pigment epithelium derived factor in diabetic nephropathy evidence for antifibrogenic activities[J]. Diabetes, 2006, 55(6):1678-1685.
[11] Cooper ME. Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy[J]. Diabetologia, 2001, 44(11):1957-1972.
[12] Sakharova OV, Taal MW, Brenner BM. Pathogenesis of diabetic nephropathy:focus on transforming growth factor-β and connective tissue growth factor[J]. Curr Opin Nephrol Hypertens, 2001, 10(6):727-738.
[13] Akai Y, Sato H, Ozaki H, et al. Association of transforming growth factor-β1 T29C polymorphism with the progression of diabetic nephropathy[J]. Am JKidney Dis, 2001, 38(4):S182-185.
[14] Basile DP. Transforming growth factor-β as a target for treatment in diabetic nephropathy[J]. Am J kidney dis, 2001, 38(4):887-890.
[15] 宋成军, 付秀美, 李健, 等. 丝胶对糖尿病肾病大鼠肾脏 TGF-β-1/Smad3 信号通路的作用[J]. 中国应用生理学杂志, 2011, 27(1):102-105.
[16] Wahab N A, Yevdokimova N, Weston BS, et al. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy[J]. Biochem J, 2001, 359(1):77-87.
[17] Hill C, Flyvbjerg A, Rasch R, et al. Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental diabetic rat kidney[J]. J Endocrinol, 2001, 170(3):647-651.
[18] Chen S, Hong SW, Iglesias-dela Cruz MC, et al. The key role of the transforming growth factor-β system in the pathogenesis of diabetic nephropathy[J]. Ren Fail, 2001, 23(3-4):471-481.
[19] 杨玉霞. 糖尿病肾病药物治疗进展[J]. 医药卫生(引文版), 2016, (2):00023-00024.
[20] 胡竞予. 黄芪联合缬沙坦治疗早期糖尿病肾病的临床观察[J]. 实用糖尿病的杂志, 2010, 6(5):41-42.
[21] 王振富, 钟灵. 姜黄素对大鼠糖尿病防治作用的实验研究[J]. 中国应用生理学杂志, 2014, 30(1):68-69.
[22] 曹红, 李军, 李广明, 等. 姜黄素对沙土鼠脑缺血/再灌注损伤的海马 CA1 区细胞凋亡和即早基因 c-fos, c-jun, NF-κB 表达变化的关系[J]. 中国应用生理学杂志, 2007, 23(2):184-188.
[23] Wu J, Li J, Cai Y, et al. Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents[J]. J Med Chem, 2011, 54:8110-8123.(上接第10页)
[15] Wu WH, Hu CP, Chen XP, et al. MicroRNA-130a mediates proliferation of vascular smooth muscle cells in hypertension[J]. Am J Hypertens, 2011, 24(10):1087-1093.
[16] Ji R, Cheng Y, Yue J, et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation[J]. Circ Res, 2007, 100(11):1579-1588.
[17] Liu X, Cheng Y, Zhang S, et al. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia[J]. Circ Res, 2009, 104(4):476-487.