Antioxidant vitamins preserve superoxide dismutase activities in gentamicin-induced nephrotoxicity

OBJECTIVE: The clinical use of gentamicin (G) is limited due to its known nephrotoxic actions. Generation of reactive oxygen species has been proposed as a causative factor of cell death in G-induced acute renal failure (ARF). Previous studies using superoxide dismutase (SOD) mimetics have indirectly suggested a role for the superoxide ion in G-induced ARF. In this study, we directly measured the enzyme activities using in situ isolated kidneys seeking to investigate the effects of antioxidant therapy on preservation of endogenous antioxidant levels in ARF. METHODS: Thirty-five male Sprague-Dawley rats were randomly assigned to 5 groups: control, Tyrode-perfused; G, gentamicin (200 mg/L) added to the perfusate; G + vitamin E (Vit E; 100 mg/100 g BW, IM); G + vitamin C (Vit C) added to the drinking water for 3 days (200 mg/L) and to the perfusate (100 mg/L); G + Vit E + Vit C. SOD activities were determined in renal tissues based on NAPDH oxidation at 340 nm by spectrophotometry. RESULTS: SOD activity was significantly reduced in the G group compared with the controls (P<.05). Administration of Vit E alone or in combination with Vit C significantly preserved enzyme activity levels compared with the G group (P<.05). CONCLUSION: Antioxidant vitamins have a role in preservation of renal endogenous antioxidant activities, namely SOD, in G-induced nephrotoxicity.     

The association of oxidant–antioxidant status in patients with chronic renal failure

Oxidative stress has been linked to disease progression, including chronic renal failure (CRF). The aim of the present study was to determine malondialdehyde (MDA) as a sign of lipid peroxidation, and to investigate the association between antioxidant activities and three trace elements, in 49 patients with CRF. The erythrocyte and plasma trace elements [selenium (Se), zinc (Zn), and copper (Cu)] and antioxidant defense levels were determined: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), vitamins E and C. The obtained values were compared with 42 age- and sex-matched healthy controls. There were significantly lower mean values of plasma Se, GPx, vitamins E and C, erythrocyte Se, SOD and CAT levels in the patient group compared to the control group (p?相似文献   

Protective effect of quercetin on renal ischemia/reperfusion injury in rats

BACKGROUND: There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. The aim of this study was to evaluate whether quercetin, an oxygen free radical scavenger, protects kidney tissue. METHODS: A renal I/R injury was induced by a left renal pedicle occlusion by ischemia for 45 min, followed by 60 mins of reperfusion with contralateral nephrectomy in rats. The rats were pretreated intraperitoneally with a quercetin suspension (50 mg/kg) 60 min before the ischemia induction. Thiobarbituric acid reactive substances (TBARS), protein carbonyl content, tumor necrosis factor alpha (TNF-alpha), reduced glutathione (GSH) levels, myeloperoxidase (MPO) catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissue. RESULTS: There were 3 groups of rats, the control group, the I/R group and the I/R+Q group. Our results indicate that TBARS, TNF-alpha levels, MPO activity and protein carbonyl content were significantly higher in the I/R group than those in the control group (p<0.05, p<0.01, p<0.01 and p<0.01, respectively). Quercetin administration significantly decreased these parameters (p<0.05, p<0.01, p<0.05 and p<0.01, respectively). GSH levels, SOD, and CAT activities significantly decreased after I/R injury when compared to the control group (p<0.01, p<0.05 and p<0.01, respectively). Quercetin treatment significantly increased GSH levels and activities of these enzymes when compared to the I/R group (p<0.05, p<0.01, p<0.05, respectively). CONCLUSIONS: These results suggest that quercetin reduces renal oxidative injury and facilitates repair. Quercetin can have a role in a renoprotective therapeutic regimen.     

Protection of preconditioning, postconditioning and combined therapy against hepatic ishemia/reperfusion injury

Objective： To study the protective effect of ischenlic preconditioning （I-pre） and ischemic postconditioning （I- post） against ischenlia/reperfusion （I/R） injury in rat＇ s liver. Methods： Using rat model of hepatic segmental I/R injury, rats were divided into 5 groups： Group A （sham group）, Group B （I/R injury）, Group C （I-pre group）, Group D （I-post group ） and Group E （combined treatment of I-pre and I-post ）. Serum alanine aminotransferase （ ALT ）, aspartate aminotransferase （ AST）, malondiaidehyde （ MDA ）, glutathione （ GSH ）, superoxide dismutase （ SOD ）, glutathione peroxidase （GSH-Px） and myeloperoxidase （MPO） in hepatic tissues were determined, respectively. In addition, 7 days＇survival of Groups B, C, D and E were evaluated. Results. Compared with Group B, Groups C, D and E exhibited significantly decreased ALT and AST release, minimized tissue injury, suppressed values of MDA and MPO, increased activities of SOD, GSH-Px and GSH （P〈0.05 ）, as well as improved animal survival. The differences among Groups C, D and E were not statistically significant. Conclusions： I-pre, I-post and combined therapy of I-pre and I-post have protective effect against hepatic I/R injury, which is correlated with its function of reducing the production of reactive oxygen species, maintaining the activities of antioxidant systems and suppressing neutrophils recruitment. No additive effect can be obtained in Group E.     

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。     

Oxidative stress, inflammation and early cardiovascular damage in children with chronic renal failure

The relationship between inflammation, oxidant stress and cardiovascular damage in children with chronic renal failure (CRF) has not previously been investigated. The aim of this study was to investigate markers of oxidative stress, inflammation and early cardiovascular abnormalities. Therefore, erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities; blood glutathione (GSH) and serum malondialdehyde (MDA) levels; C-reactive protein (CRP) and proinflammatory cytokines (IL-6, TNF-α,); and left ventricular masses (LVM) and intima media thicknesses (IMT) were measured in children with CRF. A total of 29 children with CRF (19 nondialysis, 10 peritoneal dialysis) were included. The control group consisted of 25 healthy subjects. CRF children had significantly increased IL-6, TNF-α, CRP and MDA concentrations and decreased SOD, CAT and GSH levels compared with controls (P<0.05). Nondialysis and peritoneal dialysis subgroups had similar oxidative stress and inflammation biomarkers (P>0.05). Erythrocyte CAT was positively correlated with CRP, TNF-α, and IL2-R in the study group. Positive correlations were found between cytokine concentrations, CRP and urea/creatinine levels. Significantly increased LVM and IMT values were found in CRF children (P<0.05). In conclusion, increased oxidant stress and inflammation together with early cardiovascular damage were found in CRF children. Further studies with more patients are needed to verify these results.     

The Protective Effects of Ascorbic Acid against Renal Ischemia-Reperfusion Injury in Male Rats

There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups: group 1 (control; dissection of the right renal pedicle without nephrectomy), group 2 (sham operated; unilateral nephrectomy), group 3 (I/R; unilateral nephrectomy?+?I/R); and group 4 (AA+I/R; unilateral nephrectomy and I/R treated with ascorbic acid, 250mg kg^?1 i.p., for one hour prior to ischemia). On the 15th day following nephrectomy, groups 3 and 4 were subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. At the end of the treatment period, kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.     

Antioxidative effects of exogenous nitric oxide versus antioxidant vitamins on renal ischemia reperfusion injury

The objectives of this study were to compare the protective influence of exogenous nitric oxide on renal ischemia reperfusion (I/R) injury with that of the antioxidant vitamins C and E. Sprague-Dawley rats were divided into three groups ( n=12 per group). Normal saline solution was given in group 1, a vitamin C (200 mg/kg/d) plus vitamin E (100 mg/kg/d) combination in group 2 for 3 days before operating and Na-nitroprusside (5 mg/kg/d) in group 3 before reperfusion. The left kidneys were exposed to warm ischemia for 40 min followed by reperfusion for 90 min. The right kidneys were used as internal controls. After both kidneys were removed, histopathological examinations were performed, and oxidative and antioxidative parameters were measured. In the postischemic reperfused rat kidneys, the renal lipid peroxidation level was significantly lower, and the renal GSH level higher in the group given Na-nitroprusside compared with groups 1 and 2. Renal specific xanthine oxidase activity was also significantly lower in the group treated with Na-nitroprusside than in the groups given vitamins or saline. There was a significant, negative correlation between lipid peroxidation and reduced glutathione levels. Our results suggest that the exogenous nitric oxide (Na-nitroprusside) inhibits xanthine oxidase, and has more apparent preventive features for renal I/R injury than the antioxidant vitamins C+E.     

Plasma myeloperoxidase and vitamin E levels in head injury: preliminary results related to outcome

This preliminary study was designed to assess a possible role of neutrophil activation and to determine the prognostic value of plasma myeloperoxidase (MPO) and vitamin E (Vit. E) levels in severe head injury. Plasma MPO and Vit. E levels were measured in nine severely head-injured patients (Glasgow Coma Score 相似文献   

Hyperbaric oxygenation attenuates renal ischemia-reperfusion injury in rats

BACKGROUND: Oxygen-derived free radicals play an important role in ischemia-reperfusion injury (IR). Hyperbaric oxygenation (HO) decreases free radical production. The aim of this study was to determine the effect of HO treatment on renal ischemia-reperfusion injury in rats. METHODS: Rats were divided into four groups. All groups underwent right nephrectomy. Group I served as the control group; group II had left renal ischemia-reperfusion; group III was pretreated with HO; and group IV, ischemia-reperfusion and HO pretreatment. Tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured, and histopathologic damage scored. RESULTS: HO pretreatment significantly decreased tissue MDA levels and histopathologic scores among rats with IR. There was an increased GSH in HO-pretreated rats with IR; however, the difference was not significant. CONCLUSION: HO prior to ischemia displayed a beneficial effect on renal IR by reducing oxygen radical peroxidation of lipid membranes.     

扶正泄浊保肾汤对CRF大鼠血浆ET-1、Scr、BUN及肾组织病理的影响

目的：观察扶正泄浊保肾汤对慢性肾衰竭（CRF）大鼠血浆内皮素-1（ET-1）、血肌酐（Scr）、尿素氮（BUN）及肾组织病理的影响,探讨其作用机制.方法：采用5/6肾切除的方法制造CRF模型.将60只雄性SD大鼠随机分为6组：假手术组、模型组、尿毒清组及扶正泄浊保肾汤大、中、小剂量组;分别按一定比例予大、中、小剂量组大鼠灌胃,假手术组及模型组同时间予等体积的生理盐水灌胃.所得数据均采用（±s）表示,组间比较用t检验,采用SPSS 18.0进行统计学处理.结果：各治疗组与模型组间比较,血浆ET-1及Scr、BUN水平显著下降,差异有统计学意义（P＜0.05）,且肾脏病理改变较轻;大、中剂量组与小剂量、尿毒清组间差异有统计学意义（P＜0.05）;大、中剂量组间差异无统计学意义（P＞0.05）;小剂量组与尿毒清组间差异无统计学意义（P＞0.05）.结论：扶正泄浊保肾汤具有降低大鼠血清ET-1、Scr、BUN水平,减轻肾脏病理表现的作用.     

Protective Effect of Infliximab on Ischemia/Reperfusion-Induced Damage in Rat Kidney

Objective: To investigate the protective effect of infliximab on ischemia–reperfusion (I/R) injury of the rat kidney. Methods: Twenty-eight male Wistar albino rats were divided into four groups: sham-operated, I/R, I/R with infliximab administered before ischemia [I/R + infliximab (bi)], and I/R with infliximab administered before reperfusion [I/R + infliximab (br)]. After a right nephrectomy to produce damage, the left renal vessels were occluded for 60 min, followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin–eosin (H&E)-stained and periodic acid–Schiff (PAS) sections. Results: The MDA and MPO levels in the I/R group were significantly higher than in the other groups (p < 0.05), and the SOD and GSH levels in the I/R + infliximab (bi) and I/R + infliximab (br) groups were significantly higher than in the I/R group (p < 0.05). However, histological examination revealed that the I/R + infliximab (bi) group and the I/R + infliximab (br) group had significantly fewer tubular changes and interstitial inflammatory cell infiltration than the I/R group. Conclusion: These results show that infliximab may protect against I/R injury in the rat I/R model.     

Lipid peroxidation in vitamin E-deficient rats submitted to subtotal nephrectomy

Clinical and experimental evidence has indicated that chronic renal failure (CRF) is related to increased free radical production. CRF patients show increased lipid peroxidation after a progressive reduction in vitamin E, one of the most important antioxidants. In the present study the role of vitamin E deficiency in lipid peroxidation was investigated in rats submitted to subtotal nephrectomy. Male Wistar rats were divided into groups receiving different diets for a period of 45 days: SND - sham rats submitted to a regular diet containing vitamin E; ERD nephrectomized rats submitted to a regular diet containing vitamin E; SDD - sham rats submitted to a vitamin E-deficient diet; EDD nephrectomized rats submitted to a vitamin E-deficient diet. After 30 days the Experimental animals were submitted to 5/6 nephrectomy and the Controls were submitted to sham operation. The vitamin E levels of the SDD and EDD groups were significantly reduced (p < 0.05) in plasma (4.92 +/- 1.22 and 8.37 +/- 2.09 mmol/L, respectively), liver (7.57 +/- 2.72 and 9.44 +/- 2.55mg/g tissue, respectively) and kidney (8.17 +/- 2.38 and 9.40 +/- 3.10 mg/g tissue, respectively) when compared to the SRD and ERD groups. In contrast, in the EDD group the levels of thiobarbituric acid-reactive substances, expressed as nmol/mg protein, were significantly increased (p < 0.05) in the liver (1.41 +/- 0.27) and kidney (1.67 +/- 0.47), and superoxide dismutase activity was significantly increased in the erythrocytes (4455.80 +/- 1322.63 Ug/Hb) compared to all other groups. The vitamin E-deficient diet associated with subtotal nephrectomy determined an increase in lipid peroxidation, suggesting an important role of free radicals in the development of chronic renal failure.     

Comparison of changes in tissue oxidative-stress markers in experimental model of open, laparoscopic, and retroperitoneoscopic donor nephrectomy

PURPOSE: We evaluated the oxidative stress in renal tissue during three types of surgery: open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), and retroperitoneoscopic donor nephrectomy (RDN). The aim was to find out which is the appropriate procedure for harvesting a donor kidney. MATERIALS AND METHODS: Twenty-four New Zealand White rabbits were randomized to four groups, each consisting of six rabbits. Group I (control) was subjected to 180 minutes of anesthesia, and transperitoneal nephrectomy was performed without creation of warm ischemia. In group II (ODN), after 180 minutes of anesthesia, warm ischemia was created for 5 minutes, and nephrectomy was performed. Group III (LDN) was subjected to 5 minutes of warm ischemia after 180 minutes of pneumoperitoneum at 12 mm Hg, and the kidney was removed. In group IV (RDN), after pneumoretroperitoneum at 12 mm Hg for 180 minutes, warm ischemia was created for 5 minutes, and nephrectomy was performed. Renal tissues were analyzed to determine malondialdehyde (MDA) and reduced glutathione (GSH) as oxidative-stress markers. RESULTS: Renal tissue GSH levels were decreased, whereas MDA levels were increased in groups II through IV compared with the control group (p<0.05). There was no statistically significant difference between the ODN, LDN, and RDN groups in the renal oxidative-stress markers. CONCLUSION: No differences were detected in oxidative-stress markers in renal tissue samples between ODN, LDN, and RDN. Therefore, we believe LDN and RDN can be used for live donor kidney harvesting as effectively as ODN without creating greater oxidative stress, which can have deleterious effects on a donor kidney.     

低分子右旋糖酐铁和蔗糖铁对慢性肾衰竭大鼠氧化应激的影响

目的 评价小剂量反复多次低分子右旋糖酐铁和蔗糖铁静脉用药后对慢性肾衰竭大鼠氧化应激的影响。 方法 以5/6肾大部切除术建立慢性肾衰竭大鼠模型。右肾切除术后第4周,将实验大鼠分为4组：低分子右旋糖酐铁（糖酐铁）组、蔗糖铁组、对照组、假手术组。观察6周,检测各组大鼠体内氧化应激、铁代谢等指标。 结果 糖酐铁组和蔗糖铁组大鼠血红蛋白明显高于对照组（P < 0.05）,而两铁剂组间差异无统计学意义。对照组大鼠的血清铁、血清铁蛋白、转铁蛋白饱和度显著低于假手术组（P < 0.05）;两铁剂组大鼠上述指标均显著高于对照组（P < 0.05）,而两铁剂组间差异无统计学意义。糖酐铁组和蔗糖铁组血浆晚期氧化蛋白产物（AOPP）显著高于对照组[（127.84±21.19） μmol/L、（134.21±29.38） μmol/L比 （81.83±19.93） μmol/L,P < 0.05],而两铁剂组间差异无统计学意义。两铁剂组大鼠血浆丙二醛（MDA）高于对照组,而蔗糖铁组高于糖酐铁组[（6.06±0.73） nmol/L比（4.99±0.80） nmol/L, P < 0.05]。糖酐铁组、蔗糖铁组和对照组大鼠血清超氧化物歧化酶（SOD）和总抗氧化能力（TAOC）差异无统计学意义。模型组大鼠血浆谷胱甘肽过氧化物酶（GSH-Px）水平显著低于假手术组（P < 0.05）,而蔗糖铁组显著低于糖酐铁组和对照组[（2123.11±74.78） nmol&#8226;ml-1&#8226;min-1比（2352.84±163.90） nmol&#8226;ml-1&#8226;min-1、（2310.23±125.99） nmol&#8226;ml-1&#8226;min-1,P < 0.05]。 结论 静脉补铁可部分纠正5/6肾大部切除肾衰竭大鼠的贫血,改善铁代谢指标。反复静脉小剂量补铁对慢性肾衰竭大鼠氧化应激状态有不良影响,而低分子右旋糖酐铁的不良影响低于蔗糖铁。     

高血磷对慢性肾衰竭大鼠血管钙化的影响

目的 研究高血磷对慢性肾衰竭大鼠血管钙化的影响。 方法 44只Wistar雄性大鼠分别行5/6肾切除（n=24，模型组）或假手术（n=20，对照组），39只大鼠术后4周开始给予高磷或低磷饮食10周。动物分4组：模型组+高磷饮食(CHP)，模型组+低磷饮食(CLP)，对照组+高磷饮食(NHP)，对照组+低磷饮食(NLP)。高磷饮食配方：磷（P）1.2%, 钙（Ca）1.6%，维生素D 1 IU/kg；低磷饮食配方：P 0.2%, Ca 0.5%，维生素D 1 IU/kg。特定饮食开始（基线）和结束时称体质量；检测Scr、血P、血Ca、1,25(OH)2D3、全段甲状旁腺激素（iPTH）。特定饮食结束时处死大鼠，取胸主动脉组织，采用Von Kossa染色和钙含量测定判断血管钙化程度，同时检测核心结合因子α1（Cbfα-1）mRNA的表达。 结果 术后第4周特定饮食开始时，模型组大鼠Scr水平显著高于对照组大鼠 [（94.4±17.6）比（36.4±0.6）μmol/L，P < 0.05]，余各项指标组间差异无统计学意义。特定饮食10周时，4组间体质量差异无统计学意义；各组各时间点血Ca水平差异均无统计学意义；血1,25(OH)2D3水平除了在NLP组显著增高外，余3组间差异均无统计学意义；CHP组血P和iPTH水平显著增高，出现严重血管钙化、程度3～4级；胸主动脉钙含量明显增高，同时Cbfa-1 mRNA表达显著上调。血P水平对胸主动脉钙含量的影响比iPTH水平更强（β ＝ 0.832>0.267）。血P水平与胸主动脉钙含量、Cbfα-1 mRNA表达量呈直线正相关（r = 0.672～0.73，P < 0.05）。 结论 高血磷是导致慢性肾衰竭大鼠血管钙化的重要因素。 Cbfα-1的表达上调可能是其导致血管钙化的机制之一。     

Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study

What’s known on the subject? and What does the study add? It is well known that erythropoietin (EPO) ameliorates the renal injury induced by ischemia or toxins such as cisplatin and radiocontrast media. Also, epidermal growth factor (EGF) exerts a prophylactic nephroprotective effect against the deleterious consequences of the ischemia/reperfusion (I/R) injury. Nevertheless, the combined effect of both drugs remains to be further investigated. This study examined the protective effects of EPO and EGF alone and in combination against renal I/R injury and showed that EPO alone was more powerful than EGF alone and the combination of both drugs was more protective than each agent alone.

OBJECTIVE

To investigate effects of combination of erythropoietin (EPO) and epidermal growth factor (EGF) on renal ischaemia and on reactive oxygen species in a rat model.

MATERIALS AND METHODS

In all, 90 male Sprague‐Dawley rats were allocated into five groups of 18, designated: Sham; treated with right nephrectomy only; Control, subjected to left renal ischaemia for 45 min with no treatment; EPO‐treated, as the control but with EPO pretreatment; EGF‐treated, as the control but with EGF pretreatment; EPO + EGF‐treated, as the control but with EPO and EGF pretreatment. Renal function, histopathology and malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) levels in kidneys were assessed at 1, 2 and 7 days after ischaemia.

RESULTS

All rats except the controls had a significant improvement in serum creatinine, creatinine clearance and fractional excretion of Na⁺; all three were significantly better in EPO + EGF group than in all other groups Histopathological examination showed marked structural damage in control rats. The tubular damage was least in the EPO + EGF group. The control group had a significant increase in MDA level and a significant decrease in SOD and GSH, while the EPO + EGF group had a marked significant reduction in MDA and increase in GSH and SOD.

CONCLUSION

The protection against ischaemia/reperfusion injury might be maximal when EPO and EGF are administered concomitantly, and their protective effect might be partly due to their antioxidant effects.     

抗氧化剂对去卵巢大鼠骨生物力学和血清生化指标的影响

目的 研究抗氧化剂VitC、VitE及还原璎谷光甘肽(GSH)不同配伍用药方法 对去卵巢骨质疏松症大鼠骨生物力学及血清生化指标的影响,探讨抗氧化剂不同方案对去卵巢大鼠骨质疏松症的治疗作用.方法 4个月龄雌性SD大鼠70只,随机取50只行双侧卵巢切除术,20只行假手术.3个月后随机从手术组和假手术组各取10只大鼠检测体质量、子宫湿蕈、左侧股骨及腰椎骨密度、生物力学特性和血清生化指标Ca<'2+>、肌肝(Cr)、碱性磷酸酶(ALP)水平,以确定骨质疏松模型建立成功.确定模型建立成功后,其余动物分为A(假手术)、B(去卵巢生理盐水对照组,OVX control)、C(VitC+VitE)、D(GSH)、E(VitC+VitE+GSH)五组,每组10只.VitC[750 mg/(kg·d)]、GSH[125 mg/(kg·d)]腹腔注射,VitE[250 mg/(kg·d)]灌胃,模型组每天以生理盐水腹腔注射.3个月后,检测各组动物左侧股骨及第5腰椎生物力学特性和血清生化指标. 结果 检测骨质疏松模型实验中,模型组动物同假手术组相比,体质量明显增加,子宫萎缩,子宫湿重显著降低,左侧股骨及腰椎骨密度明显降低,左侧股骨生物力学最大载荷显著降低,血清Ca<'2+>、ALP、Cr水平升高.抗氧化剂治疗3个月后,与模型组相比,治疗组D、E组左侧股骨最大载荷、弹性载荷以及第5腰椎最大载荷均明显增加;血清ALP各组均显著降低;超氧化物歧化酶(SOD)、谷光苷肽过氧化物酶(GSH-Px)水平和血清抑制OH<'->能力D、E组显著升高;丙二醛水平C、D组显著降低;各组血清Ca<'2+>水平无明显改变. 结论 抗氧化刺崩药组合GSH和GSH+VitC+VitE能明显改善骨生物力学最大载荷和弹性载荷及血清抗氧化指标抑制OH<'->能力、SOD和GSH-Px,对骨质疏松具有较显著改善作用.     

益肾降浊冲剂对5/6肾切除大鼠残肾脂质蓄积和小管间质损伤的影响

目的：观察益肾降浊冲剂对5/6肾切除大鼠残肾小管间质损伤的保护作用并探讨其机制。方法：SD雄性大鼠,随机分为假手术组、模型组、他汀组、益肾降浊冲剂组（n=8）。5/6肾切除建立慢性肾衰竭（CRF）大鼠模型,建模后2周始给药。用药8周后,检测血脂、肾功能变化,PAS染色、油红O染色、免疫组化、TUNEL染色分别观察残肾小管间质损伤评分、脂质蓄积、血凝素样氧化低密度脂蛋白受体-1（LOX-1）的表达、肾小管上皮细胞凋亡数的变化。结果：与假手术组比较,模型组大鼠尿素氮（BUN）、血肌酐（Scr）、胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、氧化低密度脂蛋白（ox-LDL）明显升高（P〈0.01）,残肾小管间质病理损伤明显加重、脂滴、LOX-1的表达、肾小管上皮细胞凋亡数均明显增高（P〈0.01）;益肾降浊冲剂干预后,与模型组比较,上述指标均明显降低（P〈0.01）。结论：益肾降浊冲剂能减轻CRF肾小管间质的损伤,其机制与纠正脂代谢紊乱、减轻肾内脂质蓄积、下调LOX-1的表达、减轻细胞凋亡有关。     

红细胞生成素对慢性肾衰竭大鼠肾小球内皮细胞功能的影响

目的 探讨红细胞生成素（EPO）对慢性肾衰竭（CRF）大鼠肾小球内皮细胞功能的影响。 方法 采用分阶段5/6肾切除术制备大鼠慢性肾衰竭动物模型。实验动物按数字随机法分为4组：假手术组（对照组）、慢性肾衰竭组（模型组）及EPO干预的两个剂量组（小剂量组EPO用量30 U/kg,大剂量组EPO用量50 U/kg）。慢性肾衰竭大鼠皮下注射EPO 6周后处死。检测各组大鼠血肌酐（Scr）、血尿素氮（BUN）、尿蛋白、血红蛋白（Hb）和血压的变化,并观察肾组织病理改变。免疫组化法检测肾小球CD34、CD31表达;RT-PCR检测肾组织内皮素1（ET-1）、内皮细胞一氧化氮合酶（eNOS）和血管内皮细胞生长因子（VEGF） mRNA的表达。 结果 与模型组比较,EPO治疗能显著增加大鼠肾小球CD34、CD31的表达（均P < 0.05）;下调肾组织ET-1 mRNA的表达（P < 0.05）;上调肾组织eNOS和 VEGF mRNA的表达（均P < 0.05）。此外,EPO治疗还能使大鼠Scr、BUN、尿蛋白和血压水平显著降低（均P < 0.05）,Hb水平显著增高（P < 0.05）,肾组织病理损害明显减轻。 结论 EPO能减轻慢性肾衰竭大鼠肾脏的病理损害,改善肾功能。这种作用可能与其促进肾小球内皮细胞的修复和改善内皮功能有关。