芹菜素对腺嘌呤所致慢性肾功能衰竭大鼠肾保护作用及机制探索
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摘要
目的研究芹菜素(APG)对腺嘌呤诱导的慢性肾功能衰竭(CRF)大鼠肾脏组织的保护作用并探索其机制。方法将100只SD大鼠按照随机数字表法随机分为正常对照组、模型组、APG低剂量组[10 mg/(kg·d)]、APG中剂量组[20 mg/(kg·d)]、APG高剂量组[40 mg/(kg·d)],每组20只;采用腺嘌呤连续灌胃21 d的方法复制CRF模型大鼠,APG各剂量组腹腔注射给药治疗,正常对照组和模型组同步给予0.9%氯化钠注射液,疗程28 d。测量24 h尿量、24 h尿蛋白量(Pro)及血清肾功能监测指标;称量体质量、肾脏质量并计算肾脏指数;HE染色法对肾脏组织进行病理学检查并进行组织病变评分;测定肾脏组织抗氧化酶活性和MDA含量,测定血清T-AOC和晚期氧化蛋白产物(AOPPs)水平;酶联免疫吸附法(ELISA)测定血清炎症细胞因子水平。结果与模型组比较,经APG中、高剂量治疗28 d后能够有效减少CRF大鼠24 h尿量和Pro,降低血清肾功能监测指标:尿素氮(BUN)、血肌酐(SCr)、尿酸(UA)含量,提高CRF大鼠体质量、降低肾脏质量并降低肾脏指数,明显改善肾脏组织病变、降低病变评分;提高肾脏组织抗氧化酶SOD、CAT活性并降低丙二醛(MDA)含量,提高血清AOPPs水平,其中高剂量组血清T-AOC水平显著提高;降低血清炎症细胞因子C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、可溶性细胞间黏附分子-1(sICAM-1)、血管间黏附分子-1(VCAM-1)水平,其中高剂量组白细胞介素-1(IL-1)水平显著降低;上述差异均具有统计学意义(P <0.05或P <0.01)。结论 APG对CRF大鼠肾组织具有一定的保护作用,其机制可能与APG降低氧化应激损伤、抑制炎症反应有关。
Objective: To investigate the protective effect and its mechanism of apigenin(APG) on renal tissue in CRF rats. Methods: 100 SD rats were randomly divided into the normal control group,the model group and APG low-dose(10 mg/kg),medium-dose(20 mg/kg),high-dose(40 mg/kg)groups(n = 20). CRF rat model was established with intragastric administration of adenine solution for 21 days;the drugs were given by intraperitoneal injection for 28 d,once a day,while the normal control group and the model group were given saline simultaneously at the same time. The 24 h urine output,24 h urine protein and the renal function monitoring indexes were determined;the body weight and kidney weight were weighted and the kidney indexes were calculated;the pathological changes of renal tissue was observed by HE staining and the lesion scores were determined;the activities of antioxidant enzymes and malondialdehyde(MDA) in renal tissue were measured;the levels of T-AOC and AOPPs in serum were measured;the levels of inflammatory cytokine in serum were measured by ELISA. Results:Compared with the model group,the 24 h urine output,24 h urine protein and the renal function monitoring indexes,such as BUN,SCr and UA,were significantly decreased in APG groups of medium-dose and high-dose;the body weight of CRF rats was increased;the weight and the indexes of kidney were decreased;the pathological changes of kidney tissue and their scores were significantly improved;the activity of SOD and CAT in kidney tissue increased,as well as the level of serum AOPPs;the content of MDA decreased;the level of serum T-AOC in high-dose group was significantly increased;the content of CRP,TNF-α,IL-6,sICAM-1 and VCAM-1 in serum were significantly decreased,and the content of IL-1 in high-dose group was significantly decreased;all the difference above were significant(P < 0.05 or P < 0.01). Conclusion: APG has a protective effect on renal tissue in CRF rats,whose mechanism may be related to APG reducing oxidative stress injury and inhibiting inflammatory response.
Objective: To investigate the protective effect and its mechanism of apigenin(APG) on renal tissue in CRF rats. Methods: 100 SD rats were randomly divided into the normal control group,the model group and APG low-dose(10 mg/kg),medium-dose(20 mg/kg),high-dose(40 mg/kg)groups(n = 20). CRF rat model was established with intragastric administration of adenine solution for 21 days;the drugs were given by intraperitoneal injection for 28 d,once a day,while the normal control group and the model group were given saline simultaneously at the same time. The 24 h urine output,24 h urine protein and the renal function monitoring indexes were determined;the body weight and kidney weight were weighted and the kidney indexes were calculated;the pathological changes of renal tissue was observed by HE staining and the lesion scores were determined;the activities of antioxidant enzymes and malondialdehyde(MDA) in renal tissue were measured;the levels of T-AOC and AOPPs in serum were measured;the levels of inflammatory cytokine in serum were measured by ELISA. Results:Compared with the model group,the 24 h urine output,24 h urine protein and the renal function monitoring indexes,such as BUN,SCr and UA,were significantly decreased in APG groups of medium-dose and high-dose;the body weight of CRF rats was increased;the weight and the indexes of kidney were decreased;the pathological changes of kidney tissue and their scores were significantly improved;the activity of SOD and CAT in kidney tissue increased,as well as the level of serum AOPPs;the content of MDA decreased;the level of serum T-AOC in high-dose group was significantly increased;the content of CRP,TNF-α,IL-6,sICAM-1 and VCAM-1 in serum were significantly decreased,and the content of IL-1 in high-dose group was significantly decreased;all the difference above were significant(P < 0.05 or P < 0.01). Conclusion: APG has a protective effect on renal tissue in CRF rats,whose mechanism may be related to APG reducing oxidative stress injury and inhibiting inflammatory response.
引文
[1]熊卫标,伍兰萼,郭倩.灯盏花最细粉对慢性肾功能衰竭大鼠保护作用的研究[J].中草药,2017,48(22):4728-4730.
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[11]陈国晓,张祥生,段小雨,等.菜素对大鼠肾脏缺血再灌注损伤的作用研究[J].中华实用诊断与治疗杂志,2017,31(10):960-962.
[12]钟瑜萍,李海燕,宫仁豪,等.大黄黄芪不同配伍比例对慢性肾衰竭大鼠24h UPQ、Scr、BUN及肾脏形态学的影响[J].中药药理与临床,2016,32(4):63-66.
[13]赵先锋.中医药治疗慢性肾衰竭研究进展[J].现代中西医结合杂志,2014,23(2):217-220.
[14]Lartigue A,Burlat B,Coutard B,et al.The megavirus chilensis Cu,Zn-superoxide dismutase:the first viral structure of a typical CCS-independent hyperstable dimeric enzyme[J].JVirol,2014,2588(14):254-261.
[15]文志勇,毛萍,金召英,等.复方黄甘提取物对慢性肾衰大鼠氧化应激的影响[J].中药材,2012,35(6):957-961.
[16]Witko-Sarat V,Friedlander M,Nguyen-Khoa T,et al.Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure[J].J Immunol,1998,161(5):2524-2532.
[17]王兴红,常陆林,王丽菲.槲皮素对糖尿病大鼠肾脏氧化应激和血清炎症相关因子的影响[J].中药药理与临床,2014,30(4):39-42.
[2]连琦,黎倩,谢媛媛,等.腺嘌呤致大鼠慢性肾功能衰竭模型研究[J].江西中医药大学学报,2016,28(6):93-97.
[3]Locatelli F,Canaud B,Eckardt KU,et al.Oxidative stress in end-stage renal disease:an emerging threat to patient outcome[J].Nephrol Dial Transplant,2003(18):1272-1278.
[4]杨婧,严睿俊,王琛,等.肾衰Ⅱ号方对慢性肾脏病患者肾功能及炎症因子的影响[J].中国中医药信息杂志,2014,21(12):15-18.
[5]陈宁.芹菜素对动脉粥样硬化大鼠氧化应激和炎性反应的影响[J].中国医药导报,2016,13(4):25-28.
[6]黄斌,陶小根,陈剑,等.芹菜素改善肥胖大鼠肾脏氧化应激损伤[J].安徽医科大学学报,2018,53(6):86-860.
[7]刘壹菲,薛晓旭,李正宜,等.芹菜素对脾细胞中树突状细胞的成熟和功能的影响[J].药学学报,2017,52(3):397-402.
[8]肖炜,马云,傅江南.慢性肾衰动物模型方法学研究现状[J].中国实验动物学杂志,2002,12(3):176-179.
[9]梁亮,王圣志,何学红.参芪泄浊饮对腺嘌呤致慢性肾衰大鼠模型肾组织细胞外基质表达影响[J].辽宁中医药大学学报,2015,17(1):27-29.
[10]黄斌,陶小根,陈剑,等.芹菜素改善肥胖大鼠肾脏氧化应激损伤[J].安徽医科大学学报,2018,53(6):856-860.
[11]陈国晓,张祥生,段小雨,等.菜素对大鼠肾脏缺血再灌注损伤的作用研究[J].中华实用诊断与治疗杂志,2017,31(10):960-962.
[12]钟瑜萍,李海燕,宫仁豪,等.大黄黄芪不同配伍比例对慢性肾衰竭大鼠24h UPQ、Scr、BUN及肾脏形态学的影响[J].中药药理与临床,2016,32(4):63-66.
[13]赵先锋.中医药治疗慢性肾衰竭研究进展[J].现代中西医结合杂志,2014,23(2):217-220.
[14]Lartigue A,Burlat B,Coutard B,et al.The megavirus chilensis Cu,Zn-superoxide dismutase:the first viral structure of a typical CCS-independent hyperstable dimeric enzyme[J].JVirol,2014,2588(14):254-261.
[15]文志勇,毛萍,金召英,等.复方黄甘提取物对慢性肾衰大鼠氧化应激的影响[J].中药材,2012,35(6):957-961.
[16]Witko-Sarat V,Friedlander M,Nguyen-Khoa T,et al.Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure[J].J Immunol,1998,161(5):2524-2532.
[17]王兴红,常陆林,王丽菲.槲皮素对糖尿病大鼠肾脏氧化应激和血清炎症相关因子的影响[J].中药药理与临床,2014,30(4):39-42.