肾缺血预处理对肾小管上皮细胞内钙超载的影响

目的：通过观察肾缺血预处理（IPC）和缺血再灌注（I/R）过程中血清超氧化物歧化酶（SOD）、丙二醛（MDA）和细胞内游离钙离子浓度（[Ca^2＋]i）含量的变化,进一步探讨肾IPC的保护机制。方法：将雄性SD大鼠88只随机分为11组,摘除右肾,分离并夹闭左肾动脉制备肾I/R和缺血预处理后缺血再灌注（IPC-I/R）动物模型。Ⅰa～Ⅴa（I/R）组为缺血再灌注0、1、24、48、72h组,Ⅰb～Ⅴb（IPC-I/R）组为缺血预处理后缺血再灌注0、1、24、48、72h组,Sham组为假手术组。比色法测定血清肌酐（Scr）、尿素氮（BUN）、SOD、MDA含量,流式细胞仪检测肾小管上皮细胞内[Ca^2＋]i水平,TUNEL原位标记法观察细胞凋亡情况。结果：除0h组外,IPC-I/R与I/R各组比较肾功能损害、细胞凋亡均明显减轻,SOD升高,MDA降低,[Ca^2＋]i水平下降;两种模型中均以再灌注24h组损伤最严重,Scr、BUN、MDA和[Ca^2＋]i水平最高,SOD水平最低,细胞凋亡最多;再灌注24h前损伤呈加重趋势,24h后逐渐减轻;组间比较,[Ca^2＋]i与血清SOD水平呈负相关,与MDA呈正相关。结论：肾IPC可以减轻I/R过程中膜脂质过氧化损伤和细胞内钙超载,从而减轻肾脏形态及功能损伤;膜脂质过氧化和细胞内钙超载相互作用,共同发挥对肾I/R损伤的保护作用。     

木兰脂素对肾缺血再灌注损伤大鼠P-选择素表达的影响

目的：探讨木兰脂素对大鼠肾缺血再灌注损伤是否具有保护作用及其可能机制。方法：雄性SD大鼠45只,随机分为假手术组、对照组和治疗组。除假手术组外,各组按再灌注时间又分为4个亚组,每组5只。治疗组和对照组分别在再灌注开始前5min静脉注射木兰脂素2mg/kg和等量生理盐水。再灌注达相应时间点时,从各亚组大鼠取血备测血肌酐（Scr）、血尿素氮（BUN）,肾组织用于观察病理变化以及作免疫组化分析肾组织P-选择素表达情况。结果：对照组BUN、Scr较假手术组明显升高,治疗组BUN、Scr较相应时间点对照组明显降低（P〈0.05）;对照组的肾组织损伤较假手术组明显加重,而治疗组的肾组织损伤较对照组明显减轻;随着时间延长,对照组肾组织P-选择素阳性表达较假手术组显著增多,治疗组肾组织P-选择素阳性表达较对照组明显减少（P〈0.05）。结论：木兰脂素对大鼠肾缺血再灌注损伤具有一定的保护作用。     

Role of iron in postischemic renal injury in the rat

To determine whether iron participates in free radical-mediated postischemic renal injury and lipid peroxidation, we examined the effects of removal of endogenous iron or provision of exogenous iron following renal ischemia, as well as the effects of renal ischemia and reperfusion on renal venous and urinary "free" iron. Rats underwent 60 minutes of renal ischemia and were studied after either 24 hours (inulin clearance) or 15 minutes (renal malondialdehyde content) of reperfusion. Infusion of the iron chelator deferoxamine (200 mg/kg/hr) during the first 60 minutes of reperfusion resulted in a marked improvement in renal function (inulin clearance: 879 +/- 154 vs. 314 +/- 74 microliter/min; P less than 0.025) and a reduction in lipid peroxidation (renal malondialdehyde: 0.449 +/- 0.06 vs. 0.698 +/- 0.08 mmol/mg prot; P less than 0.05) compared to control animals. Infusion of 50 mg/kg/hr deferoxamine also protected renal function after ischemia (inulin clearance: 624 +/- 116 vs. 285 +/- 90 microliter/min; P less than 0.05) and resulted in less histologic injury. Iron-saturated deferoxamine had no protective effect. Conversely, infusion of the iron complex EDTA-FeCl3 during reperfusion exacerbated postischemic renal dysfunction and lipid peroxidation. Following renal ischemia there was no detectable increase in "free" iron in arterial or renal venous plasma. However, urinary "free" iron increased 10- to 20-fold following reperfusion. Iron chelators which underwent filtration and gained access to this free iron in the urine (free deferoxamine or inulin-conjugated deferoxamine) provided protection, whereas a chelator confined to the vascular space (dextran-conjugated deferoxamine) did not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid peroxidation after cold storage and normothermic reperfusion: the effect of trimetazidine

Abstract Ischemia reperfusion injury is still a leading cause of early graft dysfunction after transplantation. Trimetazidine (TMZ) has been postulated to be protective against renal damage from oxygen free radicals. The aim of this study was to assess the effect TMZ during cold storage (CS) and normothermic reperfusion in an isolated perfused pig kidney model. Three groups were studied: control group, immediately perfused (GO), 48 h CS in Euro-Collins solution (G1), and 48 h CS in Euro-Collins solution plus TMZ (G2). Glomerular filtration rate (GFR) and fractional sodium reabsorption (FRNa⁺) were calculated during reperfusion from urine and perfusate samples. Lipid peroxidation was determined by the renal tissue level of Schiff bases (SB) and malondialdehyde (MDA) after reperfusion. A histological evaluation was performed after reperfusion. Renal function was significantly improved and lipid peroxidation reduced after preservation in Euro-Collins solution plus TMZ. Functional data were closely related to histological damage. In conclusion, TMZ is a useful protective agent against renal damage induced by CS.     

纤维蛋白肽Bβ15～42对大鼠缺血再灌注损伤肾脏局部炎性反应的影响

目的 观察纤维蛋白肽Bβ15～42(the fibrin-derived peptide Bβ15-42,FgBβ15～42肽)对大鼠肾脏缺血再灌注损伤(IRI)后肾脏局部炎性反应的影响并探讨其机制.方法 将SD大鼠随机分成假手术组(Sham组)、IRI组、阴性治疗组和FgBβ15 ～ 42肽治疗组.Sham组:分离肾动脉后关闭腹腔;IRI组:采用双侧肾动脉夹闭的方法制作肾脏IRI模型;阴性治疗组:于肾脏再灌注后立即尾静脉注射随机肽段3.6 mg/kg; FgBβ15～42肽治疗组:于肾脏再灌注后立即尾静脉注射FgBβ15～ 42肽3.6 mg/kg.后3组按照再灌注24h、48 h分为两个亚组,Sham组与各亚组均为8只大鼠.常规生化法检测肾功能;HE、PAS染色观察肾脏组织学改变;免疫组化、实时荧光定量PCR法及Western印迹检测肾组织白细胞介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)的mRNA及蛋白表达.结果 与Sham组相比,IRI组的Scr和BUN水平均显著增加(均P ＜0.05),肾小管及间质病理损伤显著,以再灌注48 h更为明显;与IRI组相比,FgBβ15～ 42肽治疗组Scr和BUN显著下降(均P＜0.05),小管间质损伤程度明显减轻(P＜0.05).与Sham组相比,IRI组IL-1β和ICA M-1的mRNA和蛋白水平于再灌注24h显著上升,48 h稍微下降,但仍维持在较高水平;FgBβ15～ 42肽治疗组大鼠肾组织IL-1β和ICAM-1的表达于再灌注24h、48 h显著低于同时间点的IRI组(均P＜0.05),但仍明显高于Sham组.上述各指标在阴性治疗组和IRI组之间的表达差异无统计学意义.结论 FgBβ15～42肽对肾脏IRI具有保护作用,其作用机制可能与其减少炎性因子IL-1β、黏附分子ICAM-1的表达有关.     

雷公藤内酯醇对肾缺血再灌注大鼠凋亡诱导因子及细胞间黏附分子-1表达的影响

目的:探讨雷公藤内酯醇(TP)对肾缺血再灌注(I/R)大鼠的肾保护作用,及对凋亡诱导因子、细胞间黏附分子-1的影响。方法:48只雄性Wistar大鼠随机分为假手术组、I/R模型组(I/R组)、TP高、中、低剂量干预组、泼尼松对照组(Pred组)。采用夹闭双侧肾动脉30 min,再灌注18 h的方法制作肾I/R大鼠模型。检测血肌酐(Scr)、尿素氮(BUN),原位末端标记法检测肾小管上皮细胞凋亡,观察肾病理改变,计算肾小管损伤(ATN)评分。Western印迹和RT-PCR分别检测AIF、ICAM-1蛋白和基因表达。结果:(1)I/R组血Scr、BUN、ATN评分及细胞凋亡指数较假手术组显著升高(P<0.01);与I/R组比较,TP各组以上指标均改善(P<0.01),pred组血Scr、BUN、ATN评分改善(P<0.01),但细胞凋亡指数无明显变化(P>0.05)。(2)I/R组大鼠肾组织AIF、ICAM-1较假手术组高表达(P<0.01);与I/R组比较,TP各组二者表达均减弱(P<0.01),pred组ICAM-1表达减弱(P<0.01)但AIF表达差异无统计学意义(P>0.05)。结论:TP对肾I/R大鼠具有肾保护作用,其部分机制可能与抑制肾小管上皮细胞过度凋亡及AIF、ICAM-1表达有关。     

The role of nitric oxide pathway in the renal ischemia-reperfusion injury in rats

INTRODUCTION: Nitric oxide (NO), synthesized from L-arginine by the enzyme nitric oxide synthase (NOS), seems to play an ambiguous role during tissue ischemia-reperfusion injury. Our objective was to evaluate the effects of L-arginine, a NO donor, and N(G)-nitro-L-arginine-methylester (L-NAME), a NOS inhibitor, on oxidative stress, renal dysfunction, histologic alterations and surgical mortality rate induced by renal ischemia-reperfusion (RIR) in uninephrectomized rats. MATERIALS AND METHODS: One-hundred and ninety-seven Wistar rats were randomized into five experimental groups. Group 1: sham operation; group 2: right uninephrectomy (UNI); group 3: UNI + RIR in the contralateral kidney; group 4: UNI + L-NAME (20 mg/kg; intraperitoneally) + RIR; and group 5: UNI + L-arginine + RIR. The effect of the drugs was evaluated by lipid peroxidation measured by the renal malondialdehyde (MD) content and chemiluminescence (CL) levels, serum creatinine (Cr) levels, urinary volume, tubular necrosis and athrophy, inflammatory infiltrate, interstitial fibrosis as histologic evaluation and surgical mortality rate after the procedures. A P value less than 0.05 was considered significant. RESULTS: Right uninephrectomy did not alter the renal parameters. RIR increased Cr levels (at 24 and 96 h of reperfusion), index of lipid peroxidation (both MD and QL levels), and worsened the histologic aspects. Pretreatment with L-arginine reduced the kidney levels of QL when compared with the non-treated group (5574 +/- 909 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) but increased the MD levels (0.97 +/- 0.24 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Moreover, L-arginine attenuated the increment of Cr levels, inflammatory infiltrate and tubular athrophy in rats subjected to RIR (P < 0.05). On the other hand, pretreatment with L-NAME increased both CL (17 482 +/- 4397 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) and MD levels (1.16 +/- 0.11 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Furthermore, L-NAME worsened the renal dysfunction (P < 0.05) at 192 h after the RIR, and surgical mortality rates were similar (P > 0.05). CONCLUSION: L-arginine has a tendency to exert a beneficial effect on renal damage during RIR in rats. Moreover, L-NAME seems to worsen the renal damage by increasing the kidney-levels of CL and impairment of renal function probably due to reduction of NO production.     

红景天甙对大鼠肾脏缺血再灌注损伤的保护作用

目的探讨红景天甙对大鼠肾脏缺血再灌注损伤（IRI）的预防和保护作用。方法将32只健康成年SD大鼠随机分成正常对照组、假手术组、缺血再灌注组和红景天甙组4组，每组8只。缺血再灌注组和红景天甙组分别制作肾脏缺血再灌注模型，红景天甙组予以红景天甙预处理。检测血中尿素氮（BUN）和肌酐（Scr）及肾脏中超氧化物歧化酶（SOD）、丙二酰二醛（MDA）和钠钾ATP酶（Na^＋-K^＋ATPase）含量，并用光镜和电镜观察肾脏组织形态学变化。结果红景天甙组血清BUN和Scr水平、肾皮质MDA含量较缺血再灌注组显著降低（P〈0．01），而肾皮质中SOD和Na^＋-K^＋ATPase含量与缺血再灌注组相比显著升高（P〈0．01）；肾组织光镜和电镜观察均见缺血再灌注组肾小球和肾小管上皮细胞损伤明显，而红景天甙组肾小球及肾小管仅见轻微损伤。结论红景天甙能有效降低大鼠肾脏缺血再灌注损伤（IRI），对肾脏IRI有明显的预防和保护作用，为临床上肾脏IRI提供新的预防和治疗思路。     

内皮素和降钙素基因相关肽在急性肾缺血再灌注损伤中的作用

为研究大鼠急性肾缺血再灌注损伤血液和肾组织中内皮素（ＥＴ）和降钙素基因相关肽（ＣＧＲＰ）的动态变化规律，放射免疫法检测急性肾缺血再灌注损伤大鼠血浆和肾皮质、髓质ＥＴ和ＣＧＲＰ水平变化，结果肾组织ＥＴ水平于再灌注３ｈ达到高峰，２４ｈ仍维持较高水平，肾组织ＣＧＲＰ水平再灌注２４ｈ达到高峰，血浆ＥＴ和ＣＧＲＰ于再灌注损伤后虽升高，但无显著性差异，认为肾组织ＥＴ和ＣＧＲＰ升高在急性肾缺血再灌注损伤和修复中     

The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function

BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/-0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.     

普罗布考防治大鼠顺铂急性肾损伤的实验研究

目的：复制大鼠顺铂急性肾损伤模型,研究氧化应激与核转录因子Sp1及凋亡的关系;探讨普罗布考对顺铂急性肾损伤的保护作用及作用机制。方法：24只SD雄性大鼠被随机分为生理盐水对照组、顺铂模型组、普罗布考干预组、普罗布考对照组,每组6只;检测尿N-乙酰-β-D-氨基葡萄糖甘酶（NAG）、血清肌酐（Scr）、血尿素氮（BUN）、肾组织匀浆液丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）,光镜观察肾脏病理改变;采用免疫组化染色检测肾组织Sp1蛋白表达;采用TUNEL染色检测肾小管上皮细胞凋亡。结果：与生理盐水对照组和普罗布考对照组相比,顺铂模型组大鼠血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著升高,肾组织匀浆GSH-Px活力显著下降（P〈0.01）;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显增加（P〈0.01）;肾组织Sp1蛋白的表达上调。采用普罗布考干预后血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著下降（P〈0.05）;肾组织匀浆GSH-Px活力显著升高;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显降低（P〈0.01）;肾组织Sp1蛋白的表达下调。结论：氧化应激和核转录因子Sp1在顺铂所致大鼠肾毒性中起一定作用;普罗布考对顺铂所致大鼠肾毒性有保护作用,其机制可能与抗氧化、抑制肾小管上皮细胞凋亡、下调肾组织Sp1蛋白表达有关。     

外源性硫化氢在大鼠肾脏缺血再灌注损伤中的保护作用

目的 观察不同剂量外源性硫化氢(H2S)供体硫氢化钠对大鼠肾脏缺血再灌注损伤( IRI)的保护作用.方法 健康雄性Wistar大鼠28只随机分为4组,即假手术组( Sham)、肾缺血再灌注(IR)组、硫氢化钠(NaHS)高剂量组、硫氢化钠低剂量组.大鼠右肾切除后,以NaHS作为硫化氢的供体,NaHS高、低剂量组分别经左肾动脉插管,按照1.5 μmol/min、300 nmol/min的剂量连续15 min给药,假手术组及IR组给予同体积生理盐水.停药5 min 后,NaHS组和IR组用无损伤微动脉夹夹闭左侧肾蒂45 min后解除阻断,建立大鼠急性IRI模型,假手术组不夹闭左肾动脉,其他操作同模型组.于肾脏恢复血流24h时留取血和肾组织标本,检测血清尿素氮(BUN)、血肌酐(Scr);半定量分析肾脏病理损伤;检测肾组织H2S生成率;采用实时定量PCR法检测胱硫醚-β-合成酶(CBS)、胱硫醚-γ-裂解酶(CSE )mRNA表达.结果 与假手术组相比,IR组H2S生成率显著降低(P＜0.01);CBS、CSE mRNA表达显著下降(P＜0.01 );Scr、BUN显著升高(P＜0.01);肾脏病理表现为急性肾小管坏死,且最严重.与IR组相比,NaHS预处理组H2S生成率升高(P＜0.05);CBS、CSE mRNA表达升高(P＜0.01 );Scr、BUN降低(P＜0.01);病理损伤明显减轻.NaHS两个剂量组之间差异无统计学意义.结论 外源性H2S对大鼠IRI具有保护作用.     

热休克蛋白70对肾脏缺血预处理保护作用的研究

目的 :研究缺血预处理对肾脏缺血再灌注损伤的保护作用 ,观察热休克蛋白 70 (HSP70 )的表达变化并探讨其作用机制。方法 :建立大鼠肾脏缺血再灌注损伤模型并进行缺血预处理 ,实验分组 :假手术组 (S组 )、缺血再灌注组 (IR组 )和缺血预处理组 (PC组 )。各组再灌注后检测血清肌酐 (Scr)、肾组织丙二醛 (MDA)含量 ,肾组织石蜡切片苏木精伊红染色以及免疫组化染色。结果 :PC组Scr值、肾小管病理评分、肾组织中MDA含量明显低于IR组 (P <0 .0 5 ) ,PC组与S组比较差异无显著性意义 (P >0 .0 5 ) ;HSP70免疫组化染色 :S组未见明显的阳性反应产物 ,PC组和IR组肾小管上皮细胞胞质可见棕黄色阳性反应产物。计算机图像分析显示PC组灰度值显著高于IR组 (P <0 .0 1)。结论 :缺血预处理对肾脏缺血再灌注损伤有明显保护作用 ,其作用机制可能与HSP70本身的细胞保护作用及HSP70的细胞内抗氧化作用有关     

Reduction of renal ischemia reperfusion injury by hydrogen sulfide preconditioning through inhibiting oxidative stress

Objective To investigate the possible role of oxidative stress in the protection of hydrogen sulfide during renal ischemia reperfusion. Methods Male Wistar rats were randomly divided into 3 groups: sham operation (Sham) group, renal ischemia reperfusion (IR) group subject to occlusion of left renal pedicle for 45 min then reperfusion for 24 h, and sodium hydrosulfide (NaHS) preconditioning group with continuous infusion of NaHS (450 nmol/min) by left renal artery for 10 min before ischemia reperfusion. Renal injuries were evaluated by PAS staining. The protein levels of NADPH oxidase (NOX) 4, NOX2 were analyzed by Western blotting. The reactive oxygen species (ROS) level of renal tissue was determined by dihydroethidium (DHE) staining assay. Renal superoxide dismutase (SOD), malonic dialdehyde (MDA) and Scr, BUN were evaluated by chromatometry assay. Cell apoptosis were evaluated by TdT-mediated dUTP nick end labeling (TUNEL) staining. Results Compared with Sham group, in IR group the renal NOX4 and NOX2 protein expressions, the existence of acute tubular necrosis and ROS expression were up-regulated (all P＜0.01); MDA, Scr, and BUN were increased and SOD was decreased significantly in IR-treated kidney (all P＜0.01); Moreover, more apoptotic cells presented in the risk zone of IR-treated kindey (P＜0.01). The effects induced by IR were inhibited by NaHS. Compared to that in IR group, NaHS precondition reversed IR-induced damages of renal function and renal tissue, increased SOD activity and decreased MDA expression (all P＜0.05), as well as reduced the expression of NOX4, NOX2 and ROS (all P＜0.05). Moreover, NaHS precondition reduced apoptosis after IR (P＜0.05). Conclusions NaHS alleviates renal ischemia reperfusion injury through inhibiting oxidative stress. Hydrogen sulfide can decrease ROS by inhibiting the activation of NOX, further inhibit the activation of NOD-like receptor, and alleviate kidney damage.     

Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in the rat

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). METHODS: The protective effect of N-acetylcysteine (NAC) against the damage inflicted by reactive oxygen species during renal I/R was investigated in Wistar Albino rats using biochemical parameters. Animals were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by lh of reperfusion. N-acetylcysteine (150 mg/kg, i.p.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. For biochemical analysis, the lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO) were tested. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine, was reversed by NAC. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. CONCLUSIONS: Since NAC reversed these oxidant responses, and protected rat renal proximal tubules from in vitro simulated reperfusion injury, it seems that NAC protects kidney tissue against oxidative damage.     

一氧化氮胰腺保护作用与巯基物质和氧自由基的关系

目的　探讨内源性一氧化氮 (NO)对大鼠急性坏死性胰腺炎的作用及其与巯基物质和脂质过氧化之间的关系。　方法　以 5 %牛磺胆酸钠溶液胰胆管注射 (1ml/kg)制成大鼠急性坏死性胰腺炎模型 ,以工具药L 硝基精氨酸 (L NNA)为内源性NO的阻断剂 ,观察内源性NO对胰腺损伤程度、血清淀粉酶浓度、胰腺组织内巯基物质含量和脂质过氧化终产物丙二醛 (MDA)含量的影响。　结果　牛磺胆酸钠胰胆管注射可造成胰腺组织明显的水肿和坏死 ,部分 (2 / 7)发生胰腺实质内出血 ;血清淀粉酶浓度显著升高 ,胰腺组织巯基物质含量降低 ,MDA含量增加 [(1 2 5± 0 2 8)nmol/mg蛋白质vs.(0 5± 0 0 3)nmol/mg蛋白质 ,P <0 0 5 ]。以L NNA(12 5mg/kg)阻断内源性NO ,可明显加重胰腺组织坏死 ,胰腺实质内出血率增加 (10 / 12 ,83 3 % ) ,并血清淀粉酶浓度进一步升高 ,胰腺组织MDA含量进一步增加 [(3 0± 0 40 )nmol/mg蛋白质vs.(1 2 5± 0 2 8)nmol/mg蛋白质 ,P <0 0 5 ]。但对胰腺组织内巯基物质的含量没有影响。　结论　内源性NO具有胰腺保护作用 ,其保护机制可能与抗氧自由基有关。巯基物质可能不参与NO的胰腺保护机制。     

静脉注射含饱和氢气生理盐水减轻小鼠肾脏缺血再灌注损伤

目的 研究静脉注射含饱和氢气生理盐水对小鼠肾脏缺血再灌注(IR)损伤的保护作用及其机制.方法 健康、雄性的C57BL/6小鼠随机分为3组,每组10只.假手术组(SO组)小鼠仅接受中线开腹、双侧肾蒂游离及关腹操作;缺血再灌注组(IR组)小鼠用无损伤动脉夹同时钳夹双侧肾蒂,阻断45 min,制成肾脏IR损伤模型,并于肾脏缺血同时经尾静脉注射生理盐水,5 ml/kg;实验组小鼠制成肾脏IR损伤模型,并于肾脏缺血同时经尾静脉注射含饱和氢气生理盐水,5 ml/kg.各组小鼠于肾脏再灌注6 h时检测血清尿素氮(BUN)和肌酐(Scr);检测肾组织中丙二醛(MDA)和髓过氧化物酶(MPO)的含量;观察肾脏组织形态学变化并检测肾小管上皮细胞的凋亡情况;观察肾组织中巨噬细胞的浸润情况;检测各组小鼠肾组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β和IL-17 mRNA的水平.结果 实验组血清BUN和Scr水平明显低于IR组(P<0.05).实验组肾组织病理改变较IR组明显减轻,其肾小管损伤评分明显低于IR组(P<0.01),肾小管上皮细胞凋亡明显轻于IR组(P<0.05).实验组肾组织内MDA含量低于IR组(P<0.05).实验组小鼠肾组织内中性粒细胞和巨噬细胞的浸润较IR组减少(P<0.05).实验组TNF-α、IL-6、IL-1β和IL-17mRNA的水平均低于IR组(P<0.05).结论 静脉注射含饱和氢气生理盐水能够在一定程度上减轻肾脏IR损伤,其机制可能与抑制肾脏IR后炎症反应有关.     

低温环境复灌对兔肾缺血-再灌注损伤保护作用的实验研究

目的  探讨建立兔肾缺血低温环境、常温环境及高温环境再灌注损伤模型的新方法, 并评价低温环境复灌对兔肾缺血-再灌注损伤(IRI)的影响。方法  将60只健康新西兰兔随机分为5组:对照组(A组)、假手术组(B组)、低温环境复灌组(C组)、常温环境复灌组(D组)、高温环境复灌组(E组), 每组12只。术后7 d内每日检测各组兔的血清肌酐(Scr)、血尿素氮(BUN)水平; 术后1 d检测各组兔肾组织内丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性; 术后1 d采用苏木素-伊红(HE)染色观察肾组织病理学变化; 术后1 d采用dUTP缺口末端标记(TUNEL)染色评价细胞凋亡。结果  术后1 d, 与A组和B组比较, C、D和E组兔的Scr和BUN水平均升高(均为P < 0.01);与C组比较, D组和E组兔的Scr和BUN水平升高更明显(均为P < 0.05)。术后7 d内, C、D和E组兔的Scr和BUN水平呈下降趋势。与D组和E组比较, C组兔的Scr和BUN水平较低(均为P < 0.05)。与A组和B组比较, C、D和E组的MDA含量均升高, SOD活性均降低(均为P < 0.01);与C组比较, D组和E组的MDA含量升高更明显, SOD活性更低(均为P < 0.01)。术后1 d肾组织病理学检查示A组和B组肾组织形态结构正常, D组和E组损伤表现明显, 与D、E组比较, C组损伤较轻。TUNEL染色结果显示, D组和E组肾小管上皮细胞阳性细胞明显增多, 管腔内也可见到阳性细胞, C组阳性细胞数量较D组和E组明显减少。结论  冰泥覆盖肾脏、37 ℃生理盐水及40 ℃生理盐水连续滴加肾脏可建立不同温度环境复灌模型。低温环境复灌对肾IRI具有保护作用。     

Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia-reperfusion injury in rats

Trimetazidine (TMZ), a potent antioxidant agent, has been used to protect the myocardium, liver and kidney from ischemia reperfusion (IR) injury. We investigated the effect of TMZ, a cellular anti-ischemic agent and a free radical scavenger, on 60 min of warm intestinal IR injury in rats. Sprague-Dawley rats were divided into three groups: a sham-operated group (no IR injury, n = 8), an ischemic control group (control, n = 8), and a TMZ-treated group (3 mg/kg, n = 8). Malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and mucosal damage were investigated after 120 min of reperfusion. MDA levels and MPO activity were more elevated and histopathological damage more severe in the control group than in the sham group (P < 0.05). MDA levels and MPO activity were lower and there was less histopathological damage in the TMZ group than in the control group (P < 0.05). Accumulation of lipid peroxidation products and neutrophils in mucosal tissues were significantly inhibited by TMZ treatment. We conclude that pretreatment of rats with TMZ before intestinal ischemia attenuates but does not prevent, histological damage. Received: 7 May 1998 Received after revision: 25 September 1998 Accepted: 12 October 1998     

Beneficial effects of perfusion of atrial natriuretic factor in acute post-ischemic renal insufficiency in the rat]

Owing to its capacity of increasing glomerular filtration, potential beneficial effects of atrial natriuretic factor (ANF) were assessed during a post ischemic acute renal insufficiency in rats. Renal insufficiency was obtained by clamping the renal artery during 30 min., and by performing a reperfusion during 2 hours in uninephrectomized rats. Three groups were defined: a control group where animals were submitted to an operation procedure without renal artery clamping, a control group were animals received a physiological serum perfusion (1.5 ml/h) during the renal reperfusion time and an experimental group where animals were administrated a rat 1-28 ANF perfusion (5 microns/ml in NaCl 0.9%, 1.5 ml/hour) during the reperfusion time. Insulin clearance (1.0 + 0.05 ml/h vs 0.7 + 0.05 ml/h, p < 0.01), and diuresis (32.9 +/- 3.6 microliters/min. vs 7.5 +/- 0.23 microliters/min., p < 0.01) were significantly higher in rats which were administrated a NaCl 0.9% perfusion. Histologically, a significant decrease in kidney weight and in he percentage of diseases nephrons was observed after reperfusion in ANF treated rats. The results obtained demonstrate that ANF perfusion in case of post ischemic acute renal insufficiency in rats improves the recovery of renal function and reduces the renal histologic lesions.