大蒜素对肾缺血再灌注损伤大鼠细胞凋亡的影响
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摘要
目的:探讨大蒜素对肾缺血再灌注损伤大鼠肾脏组织细胞凋亡的影响。方法:采用夹闭双侧肾蒂血管45分钟的方法建立肾缺血再灌注大鼠模型,设假手术组,模型组及大蒜素低、中、高(5、10、20 mg/kg)剂量组,每组16只,术前7天开始腹腔注射给药,1次/d;再灌注6小时后计算肾脏指数,测定血清中尿素氮(BUN)、血肌酐(SCr)和尿酸(UA)含量,观察肾脏组织形态学变化和细胞凋亡状况;测定肾脏组织中bcl-2相关X蛋白(Bax)、B细胞淋巴瘤因子2(bcl-2)、核因子κB(NF-κB)蛋白表达及抗氧化酶活性和丙二醛(MDA)含量。结果:大蒜素能降低肾缺血再灌注损伤大鼠肾脏指数,降低血清BUN、Scr、UA含量,改善肾脏组织病变和细胞凋亡状况,下调肾脏组织Bax、NF-κB蛋白表达、上调bcl-2蛋白表达、降低Bax/bcl-2比值,提高超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性并降低MDA含量,且具有一定的剂量依赖性。结论:大蒜素可能通过抑制细胞凋亡而对肾缺血再灌注损伤起到一定的保护作用,其机制可能与大蒜素能够有效调节凋亡相关基因和蛋白表达有关。
Objective: To discuss the effects of allimin on cellular apoptosis in renal tissue of the rats suffering renal ischemia/reperfusion injury(RIRI). Methods: RIRI Rat model was established by bilateral renal pedicle vessels occlusion for 45 minutes, and they were separated into sham operation group, the model group, low, moderate and high doses groups of allimin(5, 10 and 20 mg/kg), 16 rats each group, they began to accept peritoneal injection seven days before the operation, once per day, renal index was calculated after reperfusion for six hours. The contents of BUN, Scr and UA in the serum were detected, the states of cellular apoptosis and histomorphologic changes of the kidney were observed; the contents of MDA, the activity of antioxidase, protein expressions of Bax, bcl-2 and NF-kB in renal tissue were measured. Results: Allimin preconditioning could decrease renal index of RIRI rats, lower the contents of BUN, Scr and UA, improve pathoilogical changes of renal tissue and the state of cellular apoptosis,lower the expressions of Bax and NF-kB protein in renal tissue, lift the expressions of bcl-2 protein, reduce the ratio of Bax/bcl-2, improve the activity of SOD, GSH-Px and CAT, lower the contents of MDA, and they were in certain dose-dependent manner. Conclusion: Allimin might protect RIRI by inhibiting cellular apoptosis to a certain degree,and its mechanism might be related to that allimin could effectively regulate protein expressions and apoptosis-related gene.
Objective: To discuss the effects of allimin on cellular apoptosis in renal tissue of the rats suffering renal ischemia/reperfusion injury(RIRI). Methods: RIRI Rat model was established by bilateral renal pedicle vessels occlusion for 45 minutes, and they were separated into sham operation group, the model group, low, moderate and high doses groups of allimin(5, 10 and 20 mg/kg), 16 rats each group, they began to accept peritoneal injection seven days before the operation, once per day, renal index was calculated after reperfusion for six hours. The contents of BUN, Scr and UA in the serum were detected, the states of cellular apoptosis and histomorphologic changes of the kidney were observed; the contents of MDA, the activity of antioxidase, protein expressions of Bax, bcl-2 and NF-kB in renal tissue were measured. Results: Allimin preconditioning could decrease renal index of RIRI rats, lower the contents of BUN, Scr and UA, improve pathoilogical changes of renal tissue and the state of cellular apoptosis,lower the expressions of Bax and NF-kB protein in renal tissue, lift the expressions of bcl-2 protein, reduce the ratio of Bax/bcl-2, improve the activity of SOD, GSH-Px and CAT, lower the contents of MDA, and they were in certain dose-dependent manner. Conclusion: Allimin might protect RIRI by inhibiting cellular apoptosis to a certain degree,and its mechanism might be related to that allimin could effectively regulate protein expressions and apoptosis-related gene.
引文
[1]胡红林,王共先.肾缺血再灌注损伤中细胞凋亡和氧化应激[J].中国现代医学杂志,2010,20(15):2279-2283.
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[4]吴建伟,罗春丽,李家彬,等.大蒜素及缺血预处理对大鼠肾缺血再灌注损伤的影响及机制研究[J].重庆医科大学学报,2010,35(4):549-552.
[5]Chatterjee PK,Brown PA,Cuzzocrea S,et al.Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat[J].Kidney International,2001,59(6):2073-2083.
[6]Ogura T,Tanaka Y,Tamaki H,et al.Docetaxel induces Bcl-2-and pro-apoptosis caspase-independent death of human prostate cancer DU145 cells[J].Int J Oncol,2016,48(6):2330-2338.
[7]Farhadi F,Jahanpour S,Hazem K,et al.Garlic(Allium sativum)fresh juice induces apoptosis in human oral squamous cell carcinoma:the involvement of caspase-3,bax and bcl-2[J].J Dent Res Dent Clin Dent Prospects,2015,9(4):267-273.
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[9]陈良金,石孟琼,贺海波,等.珠子参总皂苷对H2O2诱导新生大鼠心肌细胞凋亡的抑制作用[J].中国临床药理学与治疗学,2012,17(8):860-867.
[10]Wided K,Hassiba R,Mesbah L.Polyphenolic fraction of algerian propolis reverses doxorubicin induced oxidative stress in liver cells and mitochondria[J].Pak J Pharm Sci,2014,27(6):1891-1897.
[11]Syed SN,Rizvi W,Kumar A,et al.In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4model[J].Afr J Tradit Complement Altern Med,2014,11(3):102-106.
[12]Cheng L,Jin Z,Zhao R,et al.Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury:role of Nrf2/AREpathway[J].Int J Clin Exp Med,2015,8(7):10420-10428.
[13]杨帆,王永青,彭余江,等.NF-κB在颅脑损伤后继发氧化应激及细胞凋亡之间的关系研究[J].浙江创伤外科,2014,19(6):899-902.
[14]Zhang Q,Huang WD,Lv XY,et al.Ghrelin protects H9c2 cells from hydrogen peroxide-induced apoptosis through NF-κB and mitochondria-mediated signaling[J].Eur J Pharmacol,2011,654(2):142-149.
[2]郭芳,邹方文,符婉,等.大蒜素对大鼠肝缺血再灌注损伤的保护作用及机制研究[J].湖南师范大学学报:医学版,2012,9(2):12-14.
[3]任丽丽,吴迪,李清君,等.大蒜素对全脑缺血/再灌注诱导的海马神经元凋亡的影响[J].中国应用生理学杂志,2007,23(4):402-403.
[4]吴建伟,罗春丽,李家彬,等.大蒜素及缺血预处理对大鼠肾缺血再灌注损伤的影响及机制研究[J].重庆医科大学学报,2010,35(4):549-552.
[5]Chatterjee PK,Brown PA,Cuzzocrea S,et al.Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat[J].Kidney International,2001,59(6):2073-2083.
[6]Ogura T,Tanaka Y,Tamaki H,et al.Docetaxel induces Bcl-2-and pro-apoptosis caspase-independent death of human prostate cancer DU145 cells[J].Int J Oncol,2016,48(6):2330-2338.
[7]Farhadi F,Jahanpour S,Hazem K,et al.Garlic(Allium sativum)fresh juice induces apoptosis in human oral squamous cell carcinoma:the involvement of caspase-3,bax and bcl-2[J].J Dent Res Dent Clin Dent Prospects,2015,9(4):267-273.
[8]Saeedi Borujeni MJ,Hami J,Haghir H,et al.Evaluation of bax and bcl-2 proteins expression in the rat hippocampus due to childhood febrile seizure[J].Iran J Child Neurol,2016,10(1):53-60.
[9]陈良金,石孟琼,贺海波,等.珠子参总皂苷对H2O2诱导新生大鼠心肌细胞凋亡的抑制作用[J].中国临床药理学与治疗学,2012,17(8):860-867.
[10]Wided K,Hassiba R,Mesbah L.Polyphenolic fraction of algerian propolis reverses doxorubicin induced oxidative stress in liver cells and mitochondria[J].Pak J Pharm Sci,2014,27(6):1891-1897.
[11]Syed SN,Rizvi W,Kumar A,et al.In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4model[J].Afr J Tradit Complement Altern Med,2014,11(3):102-106.
[12]Cheng L,Jin Z,Zhao R,et al.Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury:role of Nrf2/AREpathway[J].Int J Clin Exp Med,2015,8(7):10420-10428.
[13]杨帆,王永青,彭余江,等.NF-κB在颅脑损伤后继发氧化应激及细胞凋亡之间的关系研究[J].浙江创伤外科,2014,19(6):899-902.
[14]Zhang Q,Huang WD,Lv XY,et al.Ghrelin protects H9c2 cells from hydrogen peroxide-induced apoptosis through NF-κB and mitochondria-mediated signaling[J].Eur J Pharmacol,2011,654(2):142-149.