3种黄酮类化合物对铝染毒大鼠肝肾抗氧化系统的保护作用
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摘要
目的探讨黄酮类化合物对铝染毒大鼠肝肾抗氧化系统的保护作用。方法将64只健康SPF级雄性Wistar大鼠按体重随机分为8组,分别为阴性对照组、三氯化铝染毒组和100、200 mg/kg芦丁、葛根素、水飞蓟素拮抗组,每组8只。采用灌胃方式进行染毒,每天1次,其中,阴性对照组连续12周给予1.0 ml/d生理盐水;前4周三氯化铝染毒组和各剂量芦丁、葛根素、水飞蓟素拮抗组分别给予281.40 mg/kg三氯化铝溶液;后8周分别给予1 ml生理盐水及相应剂量的黄酮类化合物。测定大鼠肝、肾组织中的丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、ATP酶(ATPase)活力。结果与阴性对照组相比,三氯化铝染毒组大鼠肝、肾组织中的MDA含量升高,而SOD、GSH-Px活力及Na~+K~+-ATP酶、Mg~(2+)-ATP酶、Ca~(2+)-ATP酶活力均下降,差异均有统计学意义(P<0.05)。与三氯化铝染毒组比较,200 mg/kg芦丁拮抗组大鼠肝组织中的SOD活力以及200 mg/kg芦丁、葛根素拮抗组和各剂量水飞蓟素拮抗组大鼠肝组织中的GSH-Px活力均升高,差异均有统计学意义(P<0.05);而各剂量芦丁、葛根素、水飞蓟素拮抗组大鼠肝组织中的MDA含量均无明显变化。与三氯化铝染毒组比较,各剂量芦丁、葛根素、水飞蓟素拮抗组大鼠肾组织中的MDA含量均较低,而200mg/kg芦丁拮抗组大鼠肾组织中的SOD、GSH-Px活力升高,差异均有统计学意义(P<0.05)。与三氯化铝染毒组比较,200mg/kg芦丁、水飞蓟素拮抗组大鼠肝组织中的Na~+K~+-ATP酶活力及200 mg/kg芦丁、葛根素、水飞蓟素拮抗组大鼠肝组织中的Ca~(2+)-ATP酶活力以及200 mg/kg葛根素、水飞蓟素拮抗组和各剂量芦丁拮抗组大鼠肝组织中的Mg~(2+)-ATP酶活力均较高,差异有统计学意义(P<0.05)。与三氯化铝染毒组比较,200 mg/kg芦丁、水飞蓟素拮抗组大鼠肾组织中的Na~+K~+-ATP酶活力及200 mg/kg葛根素、水飞蓟素拮抗组大鼠肾组织中的Ca~(2+)-ATP酶活力以及200 mg/kg芦丁拮抗组和各剂量水飞蓟素拮抗组大鼠肾组织中的Mg~(2+)-ATP酶活力均较高,差异有统计学意义(P<0.05)。且随着芦丁、葛根素、水飞蓟素处理剂量的升高,三氯化铝染毒大鼠肝、肾组织中的MDA含量均呈下降趋势,而SOD、GSH-Px活力和Na~+K~+-ATP酶、Mg~(2+)-ATP酶、Ca~(2+)-ATP酶活力均呈上升趋势。结论黄酮类化合物(芦丁、葛根素、水飞蓟素)在一定剂量范围内对铝染毒大鼠肝肾组织抗氧化系统具有保护作用,可以有效地减轻铝造成的肝肾损伤。
Objective To investigate the protective effects of flavonoids on the antioxidation system in liver and kidney tissues of rats exposed to aluminum.Methods Sixty-four male Wistar rats were randomly divided into eight groups,eight in each,including control group,aluminum group,100 mg/kg rutin group,200 mg/kg rutin group,100 mg/kg puerarin group,200 mg/kg puerarin group,100 mg/kg silymarin group,200 mg/kg silymarin group.The tested chemicals were given through gavage once a day.The rats in control group received 1.0 ml/d saline for twelve weeks.Aluminum group and other flavonoids intervention groups metioned above received 284.1 mg/kg daily aluminum chloride(AlCl_3)hexahydrate for the first four weeks;Then for the last eight weeks,they were given 1.0 ml/d saline,and flavonoids at related doses respectively.The organ coefficients,the content of malondialdehyde(MDA),the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and ATPase in liver and kidney of rats were determined in the end of experiment.Results Aluminum intake caused significant increase of MDAand decrease of the activities of SOD,GSH-Px and ATPase compared with control group(P<0.05)in liver and kidney of rats.In liver,there were significantly higher SOD activity in the 200 mg/kg rutin group and higher GSH-Px activity in the 200 mg/kg rutin group,200 mg/kg puerarin group,silymarin groups compared with those in the AlCl_3group(P<0.05);There was no significantdifference in MDA content between the AlCl_3group and the flavonoids intervention groups.In kidney,MDA content was significantly lower in the flavonoids intervention groups,while SOD and GSH-Px activity were significantly higher in the 200mg/kg rutin group compared with those in the AlCl_3group(P<0.05).In liver,the activity of Na~+K~+-ATPase in the 200 mg/kg rutin group and 200 mg/kg silymarin group,Ca~(2+)-ATPase in all 200 mg/kg flavonoids intervention groups,Mg~(2+)-ATPase in the200 mg/kg puerarin group,200 mg/kg silymarin group and rutin groups were significantly higher compared with those in the AlCl_3group(P<0.05).In kidney,the activity of Na~+K~+-ATPase in the 200 mg/kg rutin group and 200 mg/kg silymarin group,Ca~(2+)-ATPase in the 200 mg/kg puerarin group and 200mg/kg silymarin group,Mg~(2+)-ATPase in the 200 mg/kg rutin group and silymarin groups were significantly higher compared with those in the AlCl_3group(P<0.05).With the increase of exposure doses of rutin,puerarin and silymarin,the MDA content showed a downward trend,while the levels of SOD,GSH-Px activities and Na~+K~+-ATPase,Mg~(2+)-ATPase,Ca~(2+)-ATPase showed an upward trend in liver and kidney of the intervention group.Conclusion Within certain dosage,flavonoids(rutin,puerarin,silymarin)can protect the antioxidant system in liver and kidney of rats exposed to aluminum,thus lessen the injury of liver and kidney effectively.
Objective To investigate the protective effects of flavonoids on the antioxidation system in liver and kidney tissues of rats exposed to aluminum.Methods Sixty-four male Wistar rats were randomly divided into eight groups,eight in each,including control group,aluminum group,100 mg/kg rutin group,200 mg/kg rutin group,100 mg/kg puerarin group,200 mg/kg puerarin group,100 mg/kg silymarin group,200 mg/kg silymarin group.The tested chemicals were given through gavage once a day.The rats in control group received 1.0 ml/d saline for twelve weeks.Aluminum group and other flavonoids intervention groups metioned above received 284.1 mg/kg daily aluminum chloride(AlCl_3)hexahydrate for the first four weeks;Then for the last eight weeks,they were given 1.0 ml/d saline,and flavonoids at related doses respectively.The organ coefficients,the content of malondialdehyde(MDA),the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and ATPase in liver and kidney of rats were determined in the end of experiment.Results Aluminum intake caused significant increase of MDAand decrease of the activities of SOD,GSH-Px and ATPase compared with control group(P<0.05)in liver and kidney of rats.In liver,there were significantly higher SOD activity in the 200 mg/kg rutin group and higher GSH-Px activity in the 200 mg/kg rutin group,200 mg/kg puerarin group,silymarin groups compared with those in the AlCl_3group(P<0.05);There was no significantdifference in MDA content between the AlCl_3group and the flavonoids intervention groups.In kidney,MDA content was significantly lower in the flavonoids intervention groups,while SOD and GSH-Px activity were significantly higher in the 200mg/kg rutin group compared with those in the AlCl_3group(P<0.05).In liver,the activity of Na~+K~+-ATPase in the 200 mg/kg rutin group and 200 mg/kg silymarin group,Ca~(2+)-ATPase in all 200 mg/kg flavonoids intervention groups,Mg~(2+)-ATPase in the200 mg/kg puerarin group,200 mg/kg silymarin group and rutin groups were significantly higher compared with those in the AlCl_3group(P<0.05).In kidney,the activity of Na~+K~+-ATPase in the 200 mg/kg rutin group and 200 mg/kg silymarin group,Ca~(2+)-ATPase in the 200 mg/kg puerarin group and 200mg/kg silymarin group,Mg~(2+)-ATPase in the 200 mg/kg rutin group and silymarin groups were significantly higher compared with those in the AlCl_3group(P<0.05).With the increase of exposure doses of rutin,puerarin and silymarin,the MDA content showed a downward trend,while the levels of SOD,GSH-Px activities and Na~+K~+-ATPase,Mg~(2+)-ATPase,Ca~(2+)-ATPase showed an upward trend in liver and kidney of the intervention group.Conclusion Within certain dosage,flavonoids(rutin,puerarin,silymarin)can protect the antioxidant system in liver and kidney of rats exposed to aluminum,thus lessen the injury of liver and kidney effectively.
引文
[1]刘凤贞,于德奎,刘玉镛.饮水氯化铝的神经毒效应研究[J].环境与健康杂志,1990,7(4):148-151.
[2]Liu JY,Wang Q,Sun XD,et al.The toxicity of aluminum chloride on kidney of rats[J].Biol Trace Elem Res,2016,173:339-344.
[3]任晓菲,刘萍,乔梦,等.牛磺酸对铝染毒大鼠肝功能及抗氧化系统的改善[J].环境与健康杂志,2014,31(8):679-681.
[4]胡春.黄酮类化合物的抗氧化性质[J].中国油脂,1996(4):18-21.
[5]张金桐,宋仰弟.黄酮类化合物的生物活性与电子结构关系的量子化学研究[J].山西农业大学学报:自然科学版,1993,13(2):134-140.
[6]贺小凤,杨频.黄酮类化合物的分子力学和量子化学研究[J].山西大学学报:自然科学版,1994,17(2):188-191.
[7]韩书亮.大苞雪莲四种成分抗癌作用研究[J].癌变·畸变·突变,1995,7(2):80-83.
[8]林丽莉,宋秋洁,叶翠飞,等.淫羊藿黄酮对阿尔茨海默病模型神经炎性反应的影响[J].中国康复理论与实践,2009,15(2):123-125.
[9]韩海红,马剑茵.鹰嘴豆异黄酮提取物对阿尔茨海默病模型大鼠学习记忆能力及其海马内TNF-α、IL-6表达的影响[J].中国现代应用药学,2014,31(6):689-692.
[10]苗建红,白静,李响,等.芦丁对2型糖尿病大鼠糖脂代谢及肾功能的影响[J].中药药理与临床,2014,30(6):48-51.
[11]赵春景,魏来.葛根素对CCl4所致大鼠急性肝损伤的保护作用[J].第三军医大学学报,2005(7):625-627.
[12]田图磊,洪汝涛,徐德祥,等.Egr-1在大鼠酒精性脂肪肝中的表达及水飞蓟素对其干预作用[J].安徽医药,2013,17(01):23-26.
[13]冯彤,刘萍,张震,等.1,2-二甲基-3-羟基-4-吡啶酮和牛磺酸联合干预对铝染毒大鼠大脑皮层抗氧化系统的保护作用[J].环境与健康杂志,2015,32(11):973-976.
[14]Noritsugu K,Tsuguki S,Hiromu S.Aluminum compounds enhance lipid peroxidation in liposomes:insight into cellular damage caused by oxidative stress[J].J Inorg Biochem,2007,101:967-975.
[15]Yang Y,Wang H,Guo YX,et al.Metal ion imbalance-related oxidative stress is involved in the mechanisms of liver injury in a rat model of chronic aluminum exposure[J].Biol Trace Elem Res,2016,173:126-131.
[16]Mahieu ST,Gionotti M,Millen N,et al.Effect of chronic accumulation of aluminum on renal function,cortical renal oxidative stress and cortical renal organic anion transport in rats[J].Arch Toxicol,2003,77:605-612.
[17]Hafez MM,Al-Harbi NO,Al-Hoshani AR,et al.Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats[J].Biol Res,2015,48:30.
[18]余雪源,仲英,左春旭,等.羟乙葛根素对大鼠局灶性脑缺血再灌注氧化损伤的保护作用[J].中国生化药物杂志,2012,33(1):4-7.
[19]殷利春,黄晓明,杜杭根,等.葛根素对实验性脑出血大鼠脑水肿及脂质过氧化的反应影响[J].中国中西医结合急救杂志,2004,11(6):358-360.
[20]殷利春,黄晓明,何民,等.葛根素对实验性脑出血大鼠脑组织SOD、MDA水平变化和神经功能障碍的相关性研究[J].心脑血管病防治,2010,10(5):354-355.
[21]黎荣,徐灵源,梁韬,等.葛根素对6-羟多巴胺致帕金森病模型大鼠黑质组织神经细胞的保护作用[J].中国实验方剂学杂志,2013,19(2):247-250.
[22]Wan HT,Zhu HY,Tian M,et al.Protective effect of chuanxiongzinepuerarin in a rat model of transient middle cerebral artery occlusioninduced focal cerebral ischemia[J].Nucl Med Commun,2008,29:1113-1122.
[23]李青权,周强,牛俊奇,等.水飞蓟素药理机制新进展及临床价值再探讨[J].临床肝胆病杂志,2015,31(2):315-317.
[2]Liu JY,Wang Q,Sun XD,et al.The toxicity of aluminum chloride on kidney of rats[J].Biol Trace Elem Res,2016,173:339-344.
[3]任晓菲,刘萍,乔梦,等.牛磺酸对铝染毒大鼠肝功能及抗氧化系统的改善[J].环境与健康杂志,2014,31(8):679-681.
[4]胡春.黄酮类化合物的抗氧化性质[J].中国油脂,1996(4):18-21.
[5]张金桐,宋仰弟.黄酮类化合物的生物活性与电子结构关系的量子化学研究[J].山西农业大学学报:自然科学版,1993,13(2):134-140.
[6]贺小凤,杨频.黄酮类化合物的分子力学和量子化学研究[J].山西大学学报:自然科学版,1994,17(2):188-191.
[7]韩书亮.大苞雪莲四种成分抗癌作用研究[J].癌变·畸变·突变,1995,7(2):80-83.
[8]林丽莉,宋秋洁,叶翠飞,等.淫羊藿黄酮对阿尔茨海默病模型神经炎性反应的影响[J].中国康复理论与实践,2009,15(2):123-125.
[9]韩海红,马剑茵.鹰嘴豆异黄酮提取物对阿尔茨海默病模型大鼠学习记忆能力及其海马内TNF-α、IL-6表达的影响[J].中国现代应用药学,2014,31(6):689-692.
[10]苗建红,白静,李响,等.芦丁对2型糖尿病大鼠糖脂代谢及肾功能的影响[J].中药药理与临床,2014,30(6):48-51.
[11]赵春景,魏来.葛根素对CCl4所致大鼠急性肝损伤的保护作用[J].第三军医大学学报,2005(7):625-627.
[12]田图磊,洪汝涛,徐德祥,等.Egr-1在大鼠酒精性脂肪肝中的表达及水飞蓟素对其干预作用[J].安徽医药,2013,17(01):23-26.
[13]冯彤,刘萍,张震,等.1,2-二甲基-3-羟基-4-吡啶酮和牛磺酸联合干预对铝染毒大鼠大脑皮层抗氧化系统的保护作用[J].环境与健康杂志,2015,32(11):973-976.
[14]Noritsugu K,Tsuguki S,Hiromu S.Aluminum compounds enhance lipid peroxidation in liposomes:insight into cellular damage caused by oxidative stress[J].J Inorg Biochem,2007,101:967-975.
[15]Yang Y,Wang H,Guo YX,et al.Metal ion imbalance-related oxidative stress is involved in the mechanisms of liver injury in a rat model of chronic aluminum exposure[J].Biol Trace Elem Res,2016,173:126-131.
[16]Mahieu ST,Gionotti M,Millen N,et al.Effect of chronic accumulation of aluminum on renal function,cortical renal oxidative stress and cortical renal organic anion transport in rats[J].Arch Toxicol,2003,77:605-612.
[17]Hafez MM,Al-Harbi NO,Al-Hoshani AR,et al.Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats[J].Biol Res,2015,48:30.
[18]余雪源,仲英,左春旭,等.羟乙葛根素对大鼠局灶性脑缺血再灌注氧化损伤的保护作用[J].中国生化药物杂志,2012,33(1):4-7.
[19]殷利春,黄晓明,杜杭根,等.葛根素对实验性脑出血大鼠脑水肿及脂质过氧化的反应影响[J].中国中西医结合急救杂志,2004,11(6):358-360.
[20]殷利春,黄晓明,何民,等.葛根素对实验性脑出血大鼠脑组织SOD、MDA水平变化和神经功能障碍的相关性研究[J].心脑血管病防治,2010,10(5):354-355.
[21]黎荣,徐灵源,梁韬,等.葛根素对6-羟多巴胺致帕金森病模型大鼠黑质组织神经细胞的保护作用[J].中国实验方剂学杂志,2013,19(2):247-250.
[22]Wan HT,Zhu HY,Tian M,et al.Protective effect of chuanxiongzinepuerarin in a rat model of transient middle cerebral artery occlusioninduced focal cerebral ischemia[J].Nucl Med Commun,2008,29:1113-1122.
[23]李青权,周强,牛俊奇,等.水飞蓟素药理机制新进展及临床价值再探讨[J].临床肝胆病杂志,2015,31(2):315-317.