calpain-1在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用

韩倩倩,鲁美丽,王洪新,李腾,唐富天,张英杰

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (1) : 60-63.

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (1) : 60-63. DOI: 10.13418/j.issn.1001-165x.2019.01.013
实验研究

calpain-1在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用

  • 韩倩倩1,2, 鲁美丽1, 王洪新1, 李腾3, 唐富天1, 张英杰2
作者信息 +

Role of calpain-1 in the inhibition of simvastatin on myocardial inflammation in diabetic rats

  • HAN Qian-qian 1,2, LU Mei-li 1, WANG Hong-xin 1, TANG Fu-tian1 , ZHANG Ying-jie2
Author information +
文章历史 +

摘要

目的 探讨钙蛋白酶-1(calpain-1)在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用。  方法 40只SD大鼠随机分为4组:空白对照组(CON组)、链脲佐菌素组(STZ组)、辛伐他汀高剂量(20 mg/kg)治疗组(STZ+SIM20组)及低剂量(10 mg/kg)治疗组(STZ+SIM10组),给药12周后,采用HE染色观察心肌组织病理学改变;免疫组化检测心肌组织p65的表达;Western Blot 检测心肌组织calpain-1、p65、IκBα的蛋白表达;ELISA检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量。 结果 辛伐他汀治疗组与STZ组相比,心肌细胞排列整齐,炎性细胞浸润减少;胞浆p65、IκBα蛋白表达增加,calpain-1、TNF-α、IL-6、核内p65表达减少。  结论 辛伐他汀对糖尿病大鼠心肌炎症有保护作用,其机制可能与抑制心肌calpain-1 表达有关。

Abstract

Objective To investigate the role of calpain-1 in the inhibition of simvastatin on myocardial inflammation in diabetic rats. Methods Forty SD rats were randomly divided into 4 groups: blank control group (CON group), streptozotocin group (STZ group), simvastatin high dose (20 mg/kg) treatment group (STZ+SIM20 group) and low dose (10 mg/kg) treatment group (STZ+SIM10 group). After 12 weeks, the pathological change of myocardial tissue was observed by HE staining. The expression of p65 was detected by immunohistochemistry. The expression of calpain-1, p65 and IκBα was detected by Western Blot. Serum TNF-α, IL-6 content was detected by ELISA. Results Compared with the STZ group, the SIM treatment group had neatly arranged cardiomyocytes and decreased inflammatory cell infiltration. The expression of p65 and IκBα protein in the cytoplasm was increased, and the expression of calpain-1, TNF-α, IL-6 and nucleus p65 in the nucleus was decreased. Conclusion Simvastatin has a protective effect on myocardial inflammation in diabetic rats, and its mechanism may be related to the inhibition of myocardial calpain-1 expression.

关键词

辛伐他汀 /   糖尿病大鼠 /  calpain-1 /  炎症

Key words

Simvastatin /  Diabetic rats /  Calpain-1 /  Inflammation

引用本文

导出引用
韩倩倩,鲁美丽,王洪新,李腾,唐富天,张英杰. calpain-1在辛伐他汀抑制糖尿病大鼠心肌炎症中的作用[J]. 中国临床解剖学杂志. 2019, 37(1): 60-63 https://doi.org/10.13418/j.issn.1001-165x.2019.01.013
HAN Qian-qian, LU Mei-li, WANG Hong-xin, TANG Fu-tian, ZHANG Ying-jie. Role of calpain-1 in the inhibition of simvastatin on myocardial inflammation in diabetic rats[J]. Chinese Journal of Clinical Anatomy. 2019, 37(1): 60-63 https://doi.org/10.13418/j.issn.1001-165x.2019.01.013

参考文献

[1]  Zhang B, Shen Q, Chen Y, et al. Myricitrin alleviates oxidative stress-induced inflammation and apoptosis and protects mice against diabetic cardiomyopathy[J]. Sci Rep, 2017, 7: 44239.
[2]  Miyazaki T, Koya T, Kigawa Y, et al. Calpain and atherosclerosis[J]. J Atheroscler Thromb, 2013, 20(3): 228-237.
[3] Shah MS, Brownlee M. Molecular and cellular mechanisms of cardiovascular disorders in diabetes[J]. Circ Res, 2016, 118(11): 1808-1829.
[4]  Liu J, Shen Q, Wu Y. Simvastatin prevents cardiac hypertrophy in vitro and in vivo via JAK/STAT pathway[J]. Life Sci, 2008, 82(19-20): 991-996.
[5] Al-Rasheed NM, Al-Rasheed NM, Hasan IH, et al. Simvastatin ameliorates diabetic cardiomyopathy by attenuating oxidative stress and inflammation in rats[J]. Oxid Med Cell Longev, 2017, 2017: 1092015.
[6]  陈晨 ,王洪新,张英杰,等. 黄芪甲苷通过AMPK/mTOR信号通路改善STZ诱导的糖尿病大鼠的心肌损害[J]. 中药药理与临床, 2018, 34(3): 80-85.
[7] Vulesevic B, Mcneill B, Giacco F, et al. Methylglyoxal-induced endothelial cell  loss and inflammation contribute to the development of diabetic cardiomyopathy[J]. Diabetes, 2016, 65(6): 1699-1713.
[8] Othman AI, El-sawi MR, El-missiry MA, et al. Epigallocatechin-3-gallate protects against diabetic cardiomyopathy through modulating the cardiometabolic risk factors, oxidative stress, inflammation, cell death and fibrosis in streptozotocin-nicotinamide-induced diabetic rats[J]. Biomed Pharmacother, 2017, 94: 362-373.
[9]  Seddon M, Looi YH, Shah AM. Oxidative stress and redox signalling in cardiac hypertrophy and heart failure[J]. Heart, 2007, 93(8): 903-907.
[10] Yin M, Liu Q, Yu L, et al. Downregulations of CD36 and calpain-1, inflammation, and atherosclerosis by simvastatin in apolipoprotein E knockout mice[J]. J Vasc Res, 2017, 54(3): 123-130.
[11]Choi H, Myung K. Calcitriol enhances fat synthesis factors and calpain activity in co-cultured cells[J]. Cell Biol Int, 2014, 38(8): 910-917.
[12]Li Q, Harraz MM, Zhou W, et al. Nox2 and Rac1 regulate H2O2-dependent recruitment of TRAF6 to endosomal interleukin-1 receptor complexes[J]. Mol Cell Biol, 2006, 26(1): 140-154.
[13]Li Y, Ma J, Zhu H, et al. Targeted inhibition of calpain reduces myocardial hypertrophy and fibrosis in mouse models of type 1 diabetes[J]. Diabetes, 2011, 60(11): 2985-2994.
[14]Li X, Luo R, Chen R, et al. Cleavage of IκBα by calpain induces myocardial NF-kappaB activation, TNF-alpha expression, and cardiac dysfunction in septic mice[J]. Am J Physiol Heart Circ Physiol, 2014, 306(6): H833-H843.
[15]O'neill WC, Lomashvili KA, Malluche HH, et al. Treatment with pyrophosphate inhibits uremic vascular calcification[J]. Kidney Int, 2011, 79(5): 512-517.

基金

国家自然科学基金(81870329);辽宁省自然科学基金(2015020325)


Accesses

Citation

Detail

段落导航
相关文章

/