六妙散对氟中毒大鼠自由基及肾功的影响

目的:观察投氟后不同给药组的大鼠血清中肌酐(creatimine Cr)、尿素氮(Urearutrogen BUN)、丙二醛(MDA)、超氧化物歧化酶(SOD)等水平变化。方法:48只SD大鼠,随机分为四组。给大鼠饮水投氟(每升水含氟150mg)10周,检测不同组大鼠血清中Cr、BUN、MDA、SOD的水平变化。结果:高氟组随着大鼠体内氟含量的蓄积,血清中的MDA有明显的上升趋势。血清中SOD的含量逐渐降低。与高氟组比较给予药物六妙散干扰组血清中MDA、SOD有明显差异。Cr、BUN含量高氟组与六妙散干扰组比较,数据有明显差异(P<0.05)六妙散组对氟中毒大鼠的肾功有明显的保护作用。结论:六妙散影响了氟中毒大鼠血清中MDA、SOD的含量,对氟中毒造成的肾损伤有保护作用。     

芹菜素对大鼠睾丸标志酶及氧化还原平衡的影响

本文主要探究芹菜素对雄性大鼠睾丸标志酶活力及氧化还原平衡的影响,并探讨其作用机制。通过将48只雄性SD大鼠随机分为4组,分别灌胃给予生理盐水(NS)10 mL/kg、芹菜素(AP)234、468、936 mg/kg 35 d,末次灌胃24 h后,测定大鼠睾丸标志酶及氧化还原平衡相关指标。结果发现,大鼠睾丸ACP、AKP、LDH活力及GSH含量显著降低(P0.05),Ca2+Mg2+-ATP升高(P0.05)。低剂量组SOD/(GSH-Px+CAT)降低,T-AOC升高,MDA降低(P0.05),中剂量组SOD/(GSH-Px+CAT)升高,T-AOC升高(P0.05),高剂量组SOD/(GSH-Px+CAT)升高,T-AOC降低(P0.05)。结果表明芹菜素具有抗氧化和促氧化的双重作用。本实验中AP 234、468 mg/kg主要表现为抗氧化作用,936 mg/kg表现出促氧化作用。此外,AP 234、468、936 mg/kg能降低睾丸标志酶活力。     

蝮蛇粉不同配伍方对老龄小鼠体内抗氧化的影响

目的研究蝮蛇粉不同配伍方对老龄小鼠体内抗氧化酶活性的影响。方法将10月龄ICR雄性小鼠按4%溶血液中丙二醛(MDA)水平随机分为蝮蛇粉(78mg/kg)组、蝮蛇粉+姜黄提取物(52+15.6mg/kg)组、蝮蛇粉+姜黄提取物+茶多酚(52+15.6+65mg/kg)组、阴性对照组,每组10只。各组灌胃给予相应药物,阴性对照组给予相应溶剂,每天1次,连续给药30天。采用试剂盒法检测4%溶血液中MDA水平、全血中谷胱甘肽(GSH)含量、血清中总抗氧化能力(T-AOC)和蛋白质羰基含量以及超氧化物歧化酶(SOD)的活力变化。结果与阴性对照组比较,其余各组小鼠4%溶血液中MDA水平显著降低,全血中GSH含量增加,血清蛋白质羰基含量明显降低、T-AOC含量和SOD活力显著提升(P0.05,P0.01);与蝮蛇粉组比较,蝮蛇粉+姜黄提取物组小鼠4%溶血液中MDA水平显著降低,全血中GSH含量增加,血清蛋白质羰基含量明显降低、T-AOC含量和SOD活力显著提升(P0.05,P0.01);与蝮蛇粉+姜黄提取物+茶多酚组比较,蝮蛇粉+姜黄提取物组小鼠各指标变化无明显差异。结论蝮蛇粉与姜黄提取物合用可有效改善老龄小鼠体内抗氧化能力,可起到延缓衰老作用。     

达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响*

目的:探讨达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2(GLUT2)和葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法:使用高脂饲料和一次性注射40 mg/kg链脲佐菌素(STZ)建立2型糖尿病大鼠模型,造模大鼠以空腹血糖(FBG)含量≥16.7 mmol/L时视为造模成功。造模成功后随机分为模型组(B组,生理盐水)、达格列净低剂量组(C组,0.75 mg/kg)、达格列净中剂量组(D组,1.5 mg/kg)、达格列净高剂量组(E组,3.0 mg/kg),每组6只;另选取6只健康的SD大鼠作为正常对照组(A组,生理盐水)。各组均为灌胃给药,每天1次,连续7周。灌胃给药7周后测定大鼠的体重以及血清FBG、糖化血红蛋白(HbA1c)、血尿素氮(BUN)、血肌酐(Scr)的变化;采用酶联免疫吸附测定血清及肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px);采用HE观察肾脏病理学变化;采用Western blot检测肾脏组织中GLUT2、GLUT4蛋白表达;RT-qPCR检测肾脏组织中GLUT2、GLUT4 mRNA相对表达量。结果: 与A组比较,各组大鼠的体重及SOD、GSH-PX水平明显降低(P＜ 0.05),FBG、HbA1c、BUN、Scr、MDA水平明显升高(P＜0.05),肾脏病理损伤严重,肾组织GLUT2、GLUT4 mRNA相对表达量和蛋白表达均明显降低(P均＜0.05)。与B组比较,C组、D组和E组大鼠的体重、SOD、GSH-PX水平和肾组织GLUT2、GLUT4 mRNA相对表达量明显升高(P＜0.05),FBG、HbA1c、BUN、Scr、MDA水平明显降低(P＜ 0.05);D组和E组肾脏病理损伤明显减轻,肾组织GLUT2、GLUT4蛋白表达均明显升高(P均＜0.05)。结论:达格列净可缓解2型糖尿病模型大鼠的病情,并上调肾脏GLUT2及GLUT4基因的表达。     

南瓜多糖对糖尿病大鼠血糖、血脂及氧化应激能力的影响

目的:观察南瓜多糖对实验性糖尿病大鼠血糖、血脂及氧化应激能力的影响。方法:用两次注射四氧嘧啶(alloxan)诱导糖尿病大鼠模型,将SD大鼠40只随机分为4组(n=10):即正常对照组、糖尿病组、消渴丸组和南瓜多糖组,消渴丸组用消渴丸(200 mg/kg)灌胃,南瓜多糖组行南瓜多糖(500 mg/kg)灌胃共8周,测定糖尿病大鼠血糖(BG)、血脂,测定血清中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性以及丙二醛(MDA)含量。结果:糖尿病组大鼠BG、总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)含量均升高(P0.01),高密度脂蛋白(HDL)含量降低(P0.05),SOD和CAT的活性明显降低,而MDA的含量明显增加(P0.01);消渴丸组和南瓜多糖组大鼠BG、TC、TG和LDL-C降低,HDL-C升高(P0.05),SOD和CAT的活性明显的提高,MDA的含量明显减少(P0.01)。结论:南瓜多糖具有降低糖尿病大鼠血糖、血脂和增强氧化应激能力的作用。     

硫辛酸联合缬沙坦治疗早期糖尿病肾病的疗效及安全性分析

目的:探讨硫辛酸联合缬沙坦治疗早期糖尿病肾病的疗效及安全性。方法:选取了80例糖尿病肾病患者,按随机数字表法分为两组,对照组(39例)给予缬沙坦治疗,观察组(41例)给予缬沙坦和硫辛酸治疗。通过观察并记录患者治疗前后超敏C反应蛋白(hs-CRP),尿蛋白排泄率(UAER),尿β2微球蛋白(β2-MG),血清丙二醛(MDA),总抗氧化能力(T-AOC),超氧化物歧化酶(SOD)水平及治疗期间不良反应情况,评价硫辛酸联合缬沙坦治疗早期糖尿病肾病的疗效及安全性。结果:治疗前两组hs-CRP,UEAR,β2-MG差异无统计学意义(P0.05),经2个疗程药物治疗后两组各指标均明显降低。使用硫辛酸联合缬沙坦治疗的患者,治疗后上述指标降幅更明显(P0.05),治疗前,两组SOD、MDA、T-AOC水平差异无统计学意义(P0.05),治疗后两组SOD、T-AOC水平均显著增加,MDA水平显著降低(P0.05)。组间比较,观察组SOD、T-AOC水平高于对照组,MDA水平低于对照组(P0.05);治疗期间,两组不良反应率无统计学意义(P0.05)。结论:硫辛酸联合缬沙坦能显著减少糖尿病肾病患者尿蛋白水平,改善机体氧化应激状态,用药安全,值得临床推广使用。     

还原型谷胱甘肽对阿霉素致大鼠心脏毒性的保护作用及其机制

目的:探讨还原型谷胱甘肽(GSH)对阿霉素所致大鼠心脏毒性的保护作用及其机制。方法:选取40只健康SD大鼠作为实验动物,将其随机分为4组,即GSH(小剂量)组+阿霉素组(小剂量组)、GSH(大剂量)+阿霉素组(大剂量组)、阿霉素组及生理盐水组,每组各10只。上述前3组均给予阿霉素;小剂量组给予GSH 250 mg/kg;大剂量组给予GSH 500 mg/kg;生理盐水组给予相同体积的生理盐水。末次给药24 h后,应用免疫组化学SP法检测大鼠心肌组织中BAX和BCL-2蛋白的表达情况,应用ELISA法测定大鼠血清中CK(肌酸激酶)、CK-MB(肌酸激酶同工酶)、LDH(乳酸脱氢酶)的含量以及心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)的活性,并对实验数据进行统计学分析。结果:1与阿霉素组相比,应用GSH干预的大鼠心肌组织中BCL-2的表达显著升高,BAX的表达显著降低,差异均有统计学意义(P0.05);大、小剂量组间BAX和BCL-2蛋白的表达水平比较无统计学差异(P0.05);2与阿霉素组相比,GSH干预的大鼠血清CK、CK-MB、LDH水平均显著下降,但大、小剂量组间比较无显著性差异(P0.05);3与阿霉素组相比,应用GSH干预的大鼠心肌组织MDA水平降低,SOD活力升高(P0.05),但大、小剂量组间比较无显著性差异(P0.05)。结论:还原型谷胱甘肽能够抑制阿霉素导致的心脏毒性作用,其作用机制可能与提高心肌组织BCL-2蛋白的表达与SOD水平、降低MDA水平以及BAX蛋白的表达有关。     

黄芪多糖对泌乳期奶牛抗氧化能力的影响

本实验旨在研究黄芪多糖对泌乳期荷斯坦奶牛抗氧化能力的影响。试验选取年龄、胎次和体重接近的泌乳期荷斯坦奶牛35头,随机分为5组(每组7头),各组每天分别在精料中添加0、5、10、50、100 g黄芪多糖,连续饲喂14 d。分别在第0、14和24 d采血测定血清总抗氧化能力(total antioxidant capacity,T-AOC)、超氧化物歧化酶(superoxide dismutase,SOD)活性、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性及丙二醛(malondialdehyde,MDA)含量。结果显示:在日粮中添加适量的黄芪多糖显著提高(P0.05)泌乳期奶牛血清总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GSH-Px)活性,同时显著降低(P0.05)血清中丙二醛(MDA)的含量。结果表明,日粮中添加黄芪多糖有提高泌乳期奶牛抗氧化能力的作用,适宜添加剂量在10 g~50 g/头·d。     

枸杞多糖抗氧化作用的研究

目的:研究枸杞粗多糖(Lycium Barbarum Polysaccharide,LBP)在小鼠体内的抗氧化作用。方法:用高(400mg/kg.d)、中(200mg/kg.d)、低(100mg/kg.d)剂量的枸杞粗多糖生理盐水溶液对D-半乳糖(100mg/kg.d)之衰老模型小鼠和正常小鼠灌胃。结果:枸杞粗多糖能较显著(P0.01)提高小鼠血清、肝脏及脑组织中SOD活性,降低MDA含量;极显著(P0.01)提高正常小鼠常压耐缺氧能力和游泳抗疲劳能力;此外小鼠的脾指数和胸腺指数均得到显著提高,表明枸杞粗多糖对提高小鼠的机体免疫水平具有重要的促进作用。结论:枸杞粗多糖对小鼠具有显著的抗氧化、抗衰老作用。     

人参皂苷Rg1对糖尿病肾病大鼠血清氧化应激指标、炎性因子及肾组织TGF-β1、MCP-1 mRNA的影响

目的:研究人参皂苷Rg1对糖尿病肾病(DN)大鼠血清氧化应激指标、炎性因子及肾组织生长转化因子-β1(TGF-β1)、单核细胞趋化因子蛋白-1(MCP-1)mRNA的影响。方法:选取60只SD大鼠,将其以随机抽签法分为Rg1组、模型组以及对照组,各20只。其中Rg1组与模型组大鼠均选择腹腔内一次性注射链脲佐菌素(STZ)55 mg/kg建立DN大鼠模型,Rg1组予以人参皂苷Rg1治疗,模型组与对照组则予以等量的生理盐水干预。比较干预12周后各组肾功能相关指标、血清氧化应激指标、炎性因子及肾组织TGF-β1、MCP-1 mRNA表达情况。结果:Rg1组、模型组大鼠干预12周后血肌酐(Scr)、尿素氮(BUN)、胱抑素C(CysC)水平均高于对照组,而Rg1组大鼠干预12周后Scr、BUN、CysC水平均低于模型组(均P0.05)。Rg1组、模型组大鼠干预12周后血清超氧化物歧化酶(SOD)、谷胱甘肽(GSH)水平均低于对照组,丙二醛(MDA)水平高于对照组(均P0.05);Rg1组大鼠干预12周后血清SOD、GSH水平均高于模型组,MDA水平低于模型组(均P0.05)。Rg1组、模型组大鼠干预12周后血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平均高于对照组,而Rg1组血清炎性因子水平低于模型组(均P0.05)。Rg1组、模型组大鼠干预12周后肾组织TGF-β1、MCP-1 mRNA表达水平均高于对照组,且Rg1组低于模型组(均P0.05)。结论:人参皂苷Rg1可显著改善DN大鼠血清氧化应激指标,下调血清炎性因子水平以及肾组织TGF-β1、MCP-1 mRNA表达。     

肾上腺髓质素对缺血再灌注后肾功能的保护

目的:探讨肾上腺髓质素(Adrenomedullin,ADM)对缺血再灌注后肾功能的保护作用。方法:在注射外源性ADM蛋白后,建立急性缺血再灌注肾损伤模型,观察ADM对肾功能和氧化损伤指标肌酐(Creatinine,Cr)、尿素氮(Blood Urea Nitrogen,BUN)、髓过氧化物酶(Myeloperoxidase,MPO)、丙二醛(Malondialdehyde,MDA)、超氧化物歧化酶(Superoxide Dismutase,SOD)影响。结果:与I组比较,II组的Cr、BUN、MPO、MDA大幅升高(P0.05),表明急性肾损伤造模成功。与II相比,III组BUN、MPO、MDA明显下降(P0.05),表现出一定的保护作用。结论:ADM对缺血再灌注损伤后的肾功能具有一定的保护作用,其机制可能与减少中性粒细胞浸润,抑制膜脂质的氧化,促进微血管重生修复有关。     

Apocynin Alleviates Renal Ischemia/Reperfusion Injury Through Regulating the Level of Zinc and Metallothionen

The purpose of this research was to evaluate the protective effects of apocynin on renal ischemia/reperfusion (I/R) injury (RI/RI) in rats. Rats preconditioned with apocynin were subjected to renal I/R. Zinc levels in serum and renal tissues, blood urea nitrogen (BUN), and serum creatinine (Scr) were detected. We further measured the activity of superoxide dismutase (SOD); the content of malondialdehyde (MDA), IL-4, IL-6, IL-10, and TNF-α; and the expression of metallothionein (MT) in the renal tissues. Results indicated that the levels of MDA, IL-4, IL-6, IL-10, TNF-α, and MT in the kidney tissue and serum BUN and Scr levels in RI/RI group were significantly higher than those in sham-operated group, while the levels of serum Zn and kidney Zn and SOD were reduced in RI/RI group. Apocynin treatment further decreased the levels of MDA, IL-6, TNF-α, and serum BUN and Scr, whereas it significantly increased the levels of Zn, SOD, IL-4, IL-10, and MT in the kidney tissue and serum Zn. These findings suggest that apocynin might play a protective role against RI/RI in rats through regulating zinc level and MT expression involving in oxidative stress.     

Brief small intestinal ischemia lessens renal ischemia-reperfusion injury in rats

Ischemic preconditioning (IPC) not only reduces local tissue injury caused by subsequent ischemia-reperfusion (IR) but may also have a beneficial effect on IR injury of tissues remote from those undergoing preconditioning. In this study, we investigated the effect of small intestinal IPC on renal IR injury in rats. Renal IR injury was induced by a 45-min renal artery occlusion and reperfusion for 2 or 24 h in rats with a previous contralateral nephrectomy, and ischemic preconditioning was induced by 3 cycles of 8-min ischemia and 5-min reperfusion of the small intestine. We then measured the concentrations of plasma creatinine (Cr) and blood urine nitrogen (BUN) and the level of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase (CAT) in the renal cortex. Renal histopathology also was evaluated. Pretreatment with intestinal ischemic preconditioning significantly alleviated renal IR injury, as shown by decreases in the levels of Cr, BUN, and MDA, decreased renal morphologic change, and improved preservation of SOD and CAT activities. These results suggest that remote ischemic preconditioning of the small intestine protects against renal IR injury by inhibition of lipid peroxidation and preservation of antioxidant enzyme activities.     

Role of angiotensin-converting enzyme (ACE and ACE2) imbalance on tourniquet-induced remote kidney injury in a mouse hindlimb ischemia-reperfusion model

In this study, the relationship between the local imbalance of angiotensin converting enzymes ACE and ACE2 as well as Ang II and Ang (1-7) and renal injury was observed in the different genotypes mice subjected to tourniquet-induced ischemia-reperfusion on hind limbs. In wild-type mice, renal ACE expression increased while renal ACE2 expression decreased significantly after reperfusion, accompanied by elevated serum angiotensin II (Ang II) level and lowered serum angiotensin (1-7) (Ang (1-7)) level. However, renal Ang (1-7) also increased markedly while renal Ang II was elevated. Renal injury became evident after limb reperfusion, with increased malondialdehyde (MDA), decreased super-oxide dismutase (SOD) activity and increased serum blood urea nitrogen (BUN) and creatinine (Cr), compared to control mice. These mice also developed severe renal pathology including infiltration of inflammatory cells in the renal interstitium and degeneration of tubule epithelial cells. In ACE2 knock-out mice with ACE up-regulation, tourniquet-induced renal injury was significantly aggravated as shown by increased levels of MDA, BUN and Cr, decreased SOD activity, more severe renal pathology, and decreased survival rate, compared with tourniquet-treated wild-type mice. Conversely, ACE2 transgenic mice with normal ACE expression were more resistant to tourniquet challenge as evidenced by decreased levels of MDA, BUN and Cr, increased SOD activity, attenuated renal pathological changes and increased survival rate. Our results suggest that the deregulation of ACE and ACE2 plays an important role in tourniquet-induced renal injury and that ACE2 up-regulation to restore the proper ACE/ACE2 balance is a potential therapeutic strategy for kidney injury.     

Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats

BackgroundExcessive exposure to iron can cause kidney damage, and chelating drugs such as deferoxamine and deferiprone have limited usefulness in treating iron poisoning. This study was designed to investigate the protective effects of grape seed proanthocyanidins (GSPAs) against iron overload induced nephrotoxicity in rats. The roles of GSPAs in chelating iron, antioxidant activity, renal function, pathological section, and apoptosis-related gene expression were assessed.MethodsNewly weaned male Sprague–Dawley rats aged 21 days (weight, 65 ± 5 g) were randomly divided into four groups containing 10 rats each: normal control (negative) group, iron overload (positive) group, GSPAs group, and GSPAs + iron overload (test) group. Iron dextran injections (2.5 mg⋅ kg⁻¹) and GSPAs (25 mg⋅ kg⁻¹) were intraperitoneally and intragastrically administered to rats daily for 7 weeks, respectively. Measurements included red blood cell (RBC) count and hemoglobin (Hb) level, serum total iron-binding capacity (TIBC), renal iron content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant activity (T-AOC), creatinine (CR) and blood urea nitrogen (BUN) levels, pathological changes, and apoptotic Fas, Bax expressions in the kidney tissue. Differences among the dietary groups were determined using one-way analysis of variance with post-hoc Tukey’s test. P < 0.05 was considered statistically significant.ResultsRBC count, Hb level, renal iron content, MDA content, CR and BUN levels, and Fas, Bax expressions significantly increased in the positive group than in the negative group; contrarily, TIBC, GSH-Px activity, and T-AOC significantly decreased in the positive group than in the negative group (P < 0.05). Although not statistically significant, SOD activity was slightly reduced in the positive group than in the negative group. Inflammatory cell infiltration and fibrous tissue proliferation were observed in the kidney tissue of the rats in the positive group; in contrast, the rats exhibited better recovery when GSPAs were used instead of iron alone. Compared with the positive group, RBC counts, Hb levels, renal iron contents, the MDA content, CR and BUN levels, and Fas, Bax expressions significantly decreased, whereas the TIBC, the GSH-Px and SOD activities as well as T-AOC significantly increased in the test group rats (P < 0.05). There were no significant differences in the RBC counts, Hb levels, TIBC, renal iron contents, the SOD activity and MDA content, CR and BUN levels, and Fas expression between the GSPAs and negative groups. The GSH-Px activity and T-AOC were significantly increased whereas Bax expression was significantly decreased in the GSPAs group rats than in the negative group rats (P < 0.05). The rats in the GSPAs, test, and negative groups displayed glomeruli and tubules with a clear structure; further, the epithelial cells in the renal tubules were neatly arranged.ConclusionsGSPAs have protective effects on nephrotoxicity in rats with iron overload. Thus, further investigation of GSPAs as a new and natural phytochemo-preventive agent against iron overload is warranted.     

MiR-150-5p protects against septic acute kidney injury via repressing the MEKK3/JNK pathway

BackgroundSeptic acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. MicroRNA is reportedly involved in sepsis-induced organ dysfunction, while the role of miR-150 in septic AKI remains ambiguous.MethodsQuantitative real-time PCR (qRT-PCR) was carried out to examine miR-150-5p expression in both septic AKI patients and volunteers without septic AKI. Lipopolysaccharide (LPS) was used to treat renal tubular epithelial cell line HK-2 and C57/BL6 mice to establish in vitro and in vivo sepsis-induced AKI models. Cell apoptosis was determined using TdT-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry. Cell viability was tested using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Renal pathological changes were examined via Hematoxylin-Eosin (H&E) staining, and renal function was measured via blood urea nitrogen (BUN) and creatinine (Cre) measurements. The MEKK3/JNK profile and oxidative stress markers (including COX2 and iNOS) were examined by immunoblot analysis, and the expression levels of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and oxidative stress markers (MDA, SOD, and CAT) were evaluated by ELISA.ResultsMiR-150-5p was down-regulated in the serum of patients with septic AKI (compared to healthy volunteers). Moreover, miR-150-5p levels were lower in LPS-treated HK-2 cell lines and in the septic AKI mouse model. Additionally, Stat-3 activation mediated the decrease of miR-150-5p. Functionally, miR-150-5p agomir attenuated LPS-induced apoptosis in HK-2 cells, in addition to renal inflammatory responses and oxidative stress. In contrast, inhibition of miR-150-5p aggravated LPS-induced apoptosis, inflammatory reactions and oxidative stress. Furthermore, miR-150-5p agomir decreased BUN and Scr levels in the septic AKI mice model repressed TNF-α, IL-6 and IL-1β, and up-regulated SOD and CAT down-regulated MDA in the kidney tissues. Moreover, miR-150-5p was identified as a target gene for Stat3, and the overexpression of Stat3 partially promoted the effect of down-regulating miR-150-5p on LPS-induced HK2 cell injury. Mechanistically, the MEKK3/JNK pathway was identified as a functional target of miR-150-5p, and the knockdown of MEKK3 showed protective effects against LPS mediated HK-2 cell apoptosis.ConclusionStat3-mediated miR-150-5p exerted protective effects in sepsis-induced acute kidney injury by regulating the MEKK3/JNK pathway.     

茶多酚对慢性酒精中毒大鼠肝损伤的保护作用

目的：建立慢性酒精诱导的成年大鼠肝损伤动物模型,并进行茶多酚的干预,观察茶多酚的干预对慢性酒精诱导的肝损伤大鼠的防护作用及其可能的机制。方法：将36只SD大鼠适应性喂养一周后,随机分为对照组、酒精损伤组和茶多酚干预组（每组12只）。对照组大鼠用0.9%生理盐水按7 g/kg灌胃,酒精组用体积分数56%的红星牌白酒同剂量灌胃,茶多酚干预组在酒精灌胃同时给予0.25 g/kg剂量的茶多酚。每天定时灌胃一次,连续8周。8周后处死大鼠,取内脏脂肪和肝脏组织,以脂体比衡量内脏脂肪含量,以肝体比和油红O染色结果衡量肝脂质沉积,测定超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量、总抗氧化能力（T-AOC）和谷胱甘肽过氧化物酶（GSH-Px）活力等氧化应激指标,测定肝脏组织中脂肪酸转位酶（FAT/CD36）蛋白水平。结果：与对照组相比,酒精损伤组大鼠内脏脂肪含量、SOD/MDA比值、T-AOC和GSH-Px活力显著下降（（P<0.05或P<0.01）,肝体比、FAT/CD36蛋白水平显著提高（P<0.01）,肝细胞中脂滴增加;与酒精损伤组相比,茶多酚干预组大鼠内脏脂肪含量、SOD/MDA比值、T-AOC和GSH-Px活力显著增加（（P<0.05或P<0.01）,肝体比、FAT/CD36蛋白水平显著下降（P<0.01）,肝细胞中脂滴减少。结论：茶多酚干预能改善慢性酒精中毒大鼠肝脏的脂质沉积和氧化应激状态,并伴有肝细胞膜上FAT/CD36表达的减少。     

缺血预处理对肢体缺血／再灌注肾损伤保护作用的机制初探

目的：探讨缺血预处理对肢体缺血／再灌注时肾损伤的保护作用。方法：复制家兔肢体缺血／再灌注（I／R）损伤模型,观察肢体缺血4h再灌注4h后以及应用缺血预处理干预对肾损伤的影响。分别从右颈外静脉、肾动脉和肾静脉取血,代表外周血以及入、出肾血,观察外周血超氧化物歧化酶（SOD）、丙二醛（MDA）及尿素氮（BUN）;同时测定入肾血和出肾血NO、SOD、MDA和肾组织SOD、MDA、诱导型一氧化氮合酶（iNOS）以及缺血预处理对上述指标的影响。结果：与对照组比较,缺血再灌组松夹后4h外周血、入、出肾血及肾组织SOD活性明显降低,MDA含量增高（P〈0．01）;外周血BUN以及入、出肾血NO和肾组织iNOS含量升高（P〈0．01）;在缺血前给予缺血预处理组．SOD活性升高,而MDA、BUN、NO、iNOS含量降低（P〈0．01）。相关分析显示MDA与SOD间存在明显负相关（P〈0．01）．而MDA与NO、BUN间呈显著正相关（P〈0．01）。结论：肢体缺血／再灌注时伴有肾脏氧自由基代谢紊乱,缺血预处理可以增强肾组织的抗氧化能力,对肢体缺血再灌注肾损伤具有保护作用。     

RA-XII exerts anti-oxidant and anti-inflammatory activities on lipopolysaccharide-induced acute renal injury by suppressing NF-κB and MAPKs regulated by HO-1/Nrf2 pathway

Acute kidney injury (AKI) is an abrupt loss of kidney function and severe AKI needs renal replacement therapeutic strategy and has high mortality. RA-XII is a natural cyclopeptide, isolated from the traditional Chinese medicine Rubia yunnanensis, exerting anti-inflammatory and anti-tumor activities. The present study aimed to explore the effects of RA-XII on LPS-induced ACI and the underlying molecular mechanism in TCMK-1?cells in vitro. The results indicated that RA-XII delayed the animal death caused by LPS in mice. The kidney histological changes were markedly attenuated by RA-XII. RA-XII also reduced the serum uric acid, creatinine, BUN and renal 8-OHdG. In addition, RA-XII suppressed LPS-induced oxidative stress in kidney, as evidenced by the up-regulation of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels, and the down-regulation of malondialdehyde (MDA) levels. Additionally, RA-XII enhanced heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions in renal tissue sections. Further, RA-XII reduced the release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-18, in renal, which was linked to the inhibition of inhibitor of alpha/nuclear factor kappa B (IκBα/NF-κB) and mitogen-activated protein kinases (MAPKs) pathways. The in vitro study illustrated that the anti-inflammatory effects of RA-XII were partially reversed following Nrf2 and HO-1 inhibition. Together, these findings strongly suggested that RA-XII is a potential agent against acute kidney injury.     

Protective effect of chelerythrine on gentamicin-induced nephrotoxicity

Despite their beneficial effects, aminoglycosides including gentamicin (GEN) have considerable nephrotoxic side-effects. The toxicity of GEN at the level of the kidney seems to relate to the generation of reactive oxygen species (ROS). ROS have been reported to be involved in the activation of protein kinase C (PKC). The unique structural aspects of PKC cause it to function as a sensor for oxidative stress. It seems likely that the increased NAD(P)H oxidase-derived superoxide (O2) production is at least in part mediated by PKC. We investigated the effects of chelerythrine, a commonly used PKC inhibitor, on GEN-induced changes of renal malondialdehyde (MDA), nitric oxide (NO) generation, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, glutathione (GSH) content, and serum creatinine (Cr), blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined. GEN administration to control rats increased MDA and NO generation but decreased CAT, SOD and GSH-Px activities, and GSH content. Chelerythrine administration with GEN caused significantly decreased MDA, NO generation and increased CAT, SOD and GSH-Px activities, and GSH content when compared with GEN alone. Chelerythrine also significantly decreased serum Cr and BUN levels. Morphological changes in the kidney including tubular necrosis were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of chelerythrine reduced the GEN-induced kidney damage. We propose that chelerythrine acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN via the inhibition of a PKC pathway.