芝麻素联用维生素E对化学性肾损伤大鼠eNOS/iNOS表达的影响

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (1): 24-30.

芝麻素联用维生素E对化学性肾损伤大鼠eNOS/iNOS表达的影响

宣佳利, 杨解人, 王欢, 姚海, 李伟, 赵梦秋, 韩军

皖南医学院药理学教研室,国家中医药管理局中药药理三级实验室,芜湖 241002,安徽

收稿日期:2014-09-02 修回日期:2014-11-10 发布日期:2020-07-20
通讯作者: 韩军,通信作者,男,博士,副教授,研究方向:临床药理学。Tel:0553-3932607 E-mail:aku110@163.com
作者简介:宣佳利,女,硕士在读,研究方向:临床药理学。Tel:18119886119 E-mail:478651597@qq.com
基金资助:
安徽省教育厅自然科学基金项目(kj2011B200)

Effects of sesamin combined with vitamin E on the expression of eNOS/iNOS in chemically-induced renal injury rats

XUAN Jia-li, YANG Jie-ren, WANG Huan, YAO Hai, LI Wei, ZHAO Meng-qiu, HAN Jun

Department of Pharmacology, Third-Grade Pharmacology Laboratory of State, Administration of Traditional Chinese Medicine, Wannan Medical College, Wuhu 241002, Anhui, China

Received:2014-09-02 Revised:2014-11-10 Published:2020-07-20

摘要/Abstract

摘要： 目的: 探讨芝麻素(Ses)和维生素E(VE)联用对化学性肾损伤大鼠的保护作用及其对内皮型一氧化氮合酶(eNOS)/诱导型一氧化氮合酶(iNOS)表达的影响。方法: SD大鼠28只给予D-半乳糖(D-gal,180 mg·kg^-1·d^-1,i.p.)和三氯化铝(AlCl₃,15 mg·kg^-1·d^-1,i.g.)20周建立化学性肾损伤模型。于造模第13周将大鼠随机分成模型组(生理盐水,NS,5.0 mL·kg^-1·d^-1)、Ses组(160 mg·kg^-1·d^-1)、维生素E组(VE, 10 mg·kg^-1·d^-1)及Ses +VE组(160 mg·kg^-1·d^-1+10 mg·kg^-1·d^-1),按设定剂量分别灌胃给药8周,另设正常对照组(生理盐水,NS,5.0 mL·kg^-1·d^-1,i.g.)。末次给药后称体质量(BW)和肾湿重(HWW);化学比色法测肾组织一氧化氮(NO)、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量;HE和Masson染色分别观察肾脏病理组织学和胶原纤维变化;免疫组化法测iNOS阳性细胞表达;Western Blot测eNOS蛋白表达。结果: 与模型组相比,Ses、VE 和Ses+VE组能明显减轻肾脏病理组织损伤和胶原纤维沉积;降低肾匀浆NO、MDA含量,提高T-AOC、SOD活性;上调肾脏eNOS蛋白表达,下调iNOS蛋白表达,且疗效Ses +VE组优于单用Ses、VE组(P<0.05,P<0.01)。结论: Ses 联用VE对抗化学性肾损伤大鼠的保护作用可能与其减少自由基产生,提高抗氧化能力,上调肾脏eNOS蛋白,下调iNOS蛋白,恢复eNOS/iNOS表达的异常有关,且疗效优于单用Ses和VE。

关键词: 芝麻素, 维生素E, 肾脏, 诱导型一氧化氮合酶, 内皮型一氧化氮合酶

Abstract: AIM: To investigate the protective effects of sesamin combined with vitamin E on chemically-induced renal injury and its modulation of the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rats. METHODS: Twenty-eight Sprague-Dawley (SD) rats were used to establish kidney impaired model by using D-gal (180 mg·kg^-1·d^-1,i.p.) and AlCl₃ (15 mg·kg^-1·d^-1,i.g.) for 20 weeks. A single dose of either Ses (160 mg·kg^-1·d^-1) or VE (10 mg·kg^-1·d^-1) and combined dose of Ses+VE (160 mg·kg^-1·d^-1 and 10 mg·kg^-1·d^-1) were given to rats at 13^th week post-renal injury induction for 8 consecutive weeks, while control rats were given NS (5.0 mL·kg^-1·d^-1). Bilateral kidneys from each rat were isolated to determine wet weight, nitric oxide (NO) and malondialdehyde (MDA) contents, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were also determined at the end of the experiment. Hematoxylin & eosin (HE) and Masson stain were used to observe the renal morphology and collagen deposition. Immunohistochemical technique and western blotting were employed respectively to detect the iNOS and eNOS expression. RESULTS: As compared with the model rats, the levels of NO, SOD and T-AOC were significantly increased, and the MDA content was decreased in rats treated with Ses and (or) VE. The positive expression of eNOS was apparently up-regulated by down-regulating the iNOS level and the effects of Ses plus VE was better than single Ses or VE group(P<0.05,P<0.01). CONCLUSION: The renoprotective effect ofsesamin combined with vitamin E on chemically-induced renal injury in rats could be associated with decrease in free radical generation, increase in anti-oxidant activity, promotion of eNOS, inhibition of iNOS activity, restoration of eNOS/iNOS balance, Ses plus VE treatment was more effective than Ses or VE given as a single treatment (monotherapy).

Key words: sesamin, vitamin E, kidney, iNOS, eNOS

中图分类号:

R965.2

宣佳利, 杨解人, 王欢, 姚海, 李伟, 赵梦秋, 韩军. 芝麻素联用维生素E对化学性肾损伤大鼠eNOS/iNOS表达的影响[J]. 中国临床药理学与治疗学, 2015, 20(1): 24-30.

XUAN Jia-li, YANG Jie-ren, WANG Huan, YAO Hai, LI Wei, ZHAO Meng-qiu, HAN Jun. Effects of sesamin combined with vitamin E on the expression of eNOS/iNOS in chemically-induced renal injury rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(1): 24-30.

参考文献

[1] 杜少陵, 杨解人, 张俊秀, 等. 芝麻素对自发性高血压大鼠肾病的保护作用[J]. 中国临床药理学与治疗学, 2012, 17(5): 502-507.
[2] Miyawaki T, Aono H, Toyoda-Ono Y, et al. Antihypertensive effects of sesamin in humans[J]. J Nutr Sci Vitaminol, 2009, 55(1): 87-91.
[3] Rasheed NA, Abdel Baky NA, Shebly W, et al. Effect of vitamin E and α-lipoic acid on nano zinc oxide induced renal cytotoxicity in Rats [J]. Afr J Pharm Pharmacol, 2012, 6:2211-2223.
[4] Hemalatha S, Rao MV. Sesame lignans enhance antioxidant activity of vitamin E in lipid peroxidation systems [J]. Mol Cell Biochem, 2004, 262(1/2):195-202.
[5] Ikeda S, Tohyama T, Yamashita K. Dietary sesame seed and its lignans inhibit 2, 7, 8-trimethyl-2 (2′-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed γ-tocopherol [J]. J Nutr, 2002, 132(5):961-966.
[6] 杨解人, 吴向起, 周勇, 等. 芝麻素与维生素 E 联用对代谢综合征大鼠肾病的协同保护作用[J]. 中国临床药理学与治疗学, 2009, 14(6): 629-636.
[7] Park S, Kim CS, Lee J, et al. Effect of Regular Exercise on the Histochemical Changes of D-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats [J]. Acta Histochem Cytochem, 2013, 46(4):111-119.
[8] Dlugaszek M, Fiejka M A, Graczyk A, et al. Effects of various aluminium compounds given orally to mice on Al tissue distribution and tissue concentrations of essential elements[J]. Pharmacol Toxicol, 2000, 86(3): 135-139.
[9] Schmidt AM, Du Yan S, Wautier JL, et al. Activation of receptor for advanced glycation end products a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis[J]. Circ Res, 1999, 84(5): 489-497.
[10] del Carmen Contini M, Millen N, González M, et al. Melatonin prevents oxidative stress in ovariectomized rats treated with aluminium [J]. Biol Trace Elem Res, 2011, 144(1/2/3): 924-943.
[11] Choe W, Kim S, Hwang TS, et al. Expression of inducible nitric oxide synthase in thyroidneoplasms:Immunohistochemical and molecular analysis [J]. Pathol Int, 2003, 53(7):434-439.
[12] Tian J, Yan Z, Wu Y, et al. Inhibition of iNOS protects endothelial-dependent vasodilation in aged rats [J]. Acta Pharmacol Sin, 2010, 31(10): 1324-1328.
[13] Griscavage JM, Hobbs AJ, Ignarro LJ. Negative modulation of nitric oxide synthase by nitric oxide and nitroso compounds[J]. Adv Pharmacol, 1995, 34:215-234.
[14] Zhang J, Li J, Wang L, et al. Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS [J]. J Huazhong Univ Sci Technolog Med Sci, 2014, 34(4): 516-520.

[1]	许宜琪, 吴茜, 刘书, 刘帆, 邢春燕, 李勤, 何俊俊, 何春玲, 赵咏莉, 高家林. 雷公藤多苷治疗糖尿病肾脏病的临床疗效及抗炎抗纤维化分析[J]. 中国临床药理学与治疗学, 2023, 28(9): 1034-1042.
[2]	宁思思, 赵玉红, 颜蕾, 唐敏娜, 张凝之, 张泳巧, 崔兆强. 高血压合并慢性肾脏病患者的降压目标之争议[J]. 中国临床药理学与治疗学, 2023, 28(4): 463-467.
[3]	杨治安, 赵岩, 何瑶, 刘维英, 余勤. 细胞焦亡介导慢性间歇缺氧大鼠肾脏损伤及依达拉奉的干预作用[J]. 中国临床药理学与治疗学, 2023, 28(1): 10-18.
[4]	丁嘉敏, 王友娣, 赵夏丽, 姜根风, 陈思文, 洪程程, 李书勤, 胡卫华. 生长激素和维生素E联合应用治疗薄型子宫内膜的研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 857-862.
[5]	王香溢, 盛洁, 王秀, 郭岩, 陈志武. UPLC-MS/MS法测定氘代氯化琥珀胆碱在大鼠体内分布[J]. 中国临床药理学与治疗学, 2021, 26(3): 271-277.
[6]	杨沿浪，李燕，汪琳. 肾脏内科住院患者感染病原菌分布及耐药性分析[J]. 中国临床药理学与治疗学, 2020, 25(2): 203-208.
[7]	张俊秀, 沈媛媛, 杨解人, 郑书国, 郝伟. 联用芝麻素和维生素E抑制PI3K/AKT信号通路改善自发性高血压大鼠的左室纤维化[J]. 中国临床药理学与治疗学, 2020, 25(11): 1214-1222.
[8]	郝伟，沈媛媛，张俊秀，杨解人. 芝麻素联用维生素E对自发性高血压大鼠心肌细胞凋亡的影响[J]. 中国临床药理学与治疗学, 2018, 23(11): 1221-1227.
[9]	王荣俊，丁波. 人urotensinⅡ对大鼠心肌缺血缺氧性损伤的保护作用机制[J]. 中国临床药理学与治疗学, 2017, 22(6): 622-626.
[10]	王欢，杨解人，张俊秀，姚海，马同军. 芝麻素对阿尔茨海默病大鼠学习记忆及海马谷氨酸表达的影响[J]. 中国临床药理学与治疗学, 2017, 22(5): 507-511.
[11]	卢毅宁，沈媛媛，杨解人. 芝麻素对自发性高血压大鼠海马nNOS和NADPH氧化酶亚单位p22phox、p47phox蛋白表达的调节作用[J]. 中国临床药理学与治疗学, 2016, 21(9): 989-994.
[12]	沈水娟，王时敏，李青华，邱杰山，吴国水，官继超，胡作祥. 大黄附子方延缓3-4期慢性肾脏病患者肾功能进展的研究[J]. 中国临床药理学与治疗学, 2016, 21(8): 931-934.
[13]	韩军，宣佳利，杨解人，李伟，赵梦秋. 芝麻素减轻自发性高血压大鼠肾脏纤维化作用及其机制研究[J]. 中国临床药理学与治疗学, 2016, 21(1): 16-22.
[14]	周露萍, 陈露露, 周宏灏, 欧阳冬生. IV型胶原蛋白与肾脏疾病[J]. 中国临床药理学与治疗学, 2015, 20(9): 1060-1065.
[15]	王军会, 李玉红, 茹国美, 丁倩男. 成人与儿童乳酸林格氏液液体动力学的比较[J]. 中国临床药理学与治疗学, 2015, 20(8): 909-914.