Fungal metabolite nigerloxin ameliorates diabetic nephropathy and gentamicin-induced renal oxidative stress in experimental rats

Elevated polyol pathway enzyme activities and oxidative stress play an important role in the development and progression of diabetic nephropathy. Here, we investigated the beneficial influence of nigerloxin, a fungal metabolite and a potent aldose reductase inhibitor and free radical scavenger in the kidney of streptozotocin-induced diabetic rats. A group of diabetic rats was orally administered with nigerloxin for 30 days (100 mg/kg). Diabetic rats showed increased lipid peroxides, advanced glycation end products (AGEs), elevated activities of polyol pathway enzymes, and lowered antioxidant defense system in kidney. Administration of nigerloxin decreased kidney lipid peroxides and AGEs. Activities of polyol pathway enzymes were reduced while activities of all antioxidant enzymes, glutathione, and ascorbic acid were elevated in the kidney of nigerloxin-treated diabetic rats. We also investigated antioxidant potential of nigerloxin in gentamicin-induced nephrotoxicity in Wistar rats. Groups of rats were orally administered with nigerloxin for 8 days (25 mg or 100 mg kg^?1 body weight day^?1) along with gentamicin (80 mg/kg, i.p., for 8 days). Gentamicin induced increase in lipid peroxides, decrease in glutathione and activities of antioxidant enzymes in the kidney, and increase in blood creatinine, and urea concentrations were significantly countered by nigerloxin treatment. Thus, the results indicated the beneficial influence of nigerloxin on polyol pathway and oxidative stress associated with diabetes, which are implicated in ameliorating the development of diabetic nephropathy. Nigerloxin also ameliorated oxidative stress induced by gentamicin in the renal tissue.     

FK506 ameliorates renal injury in early experimental diabetic rats induced by streptozotocin

Calcineurin (CaN) plays an important role in glomerular hypertrophy and extracellular matrix accumulation in early diabetic nephropathy. Cyclosporine (CSA), a CaN inhibitor, has been shown to reduce renal injury in streptozotocin-induced diabetic rats. We examined whether FK506, which immunosuppressive action was 10–100 times of CSA, inhibits progression of diabetic nephropathy in experimental diabetic rats. Diabetes was induced with streptozotocin in rats, and FK506 (0.5 or 1.0 mg/kg) was orally administered once a day for 4 weeks. Increased relative kidney weight was significantly reduced by FK506 treatment with 1.0 mg/kg (p < 0.05), and elevated 24 hour urinary albumin excretion rate was markedly attenuated by FK506 treatment with 0.5 and 1.0 mg/kg (p < 0.05, 0.01). Elevated glomerular volume was significantly attenuated by FK506 treatment with 0.5 and 1.0 mg/kg (p < 0.05), and increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0 mg/kg (p < 0.01). Western blot analysis noted that the expression of CaN protein was increased 2.4 fold in the kidney from diabetic rats, and FK506 treatment with 0.5 and 1.0 mg/kg could reduce increased expression of CaN protein by 38.0% and 73.2%. The expression of 1α (IV) collagen, p65, p-p65, OPN, α-SMA and TGF-β1 protein in kidney was significantly increased in diabetic rats and reduced by FK506 treatment (p < 0.05, 0.01). Our results show that FK506 could ameliorate renal injury in early experimental diabetic rats, which mechanism may be at least partly correlated with suppression on increased CaN in renal tissue in diabetic rats.     

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress,pro-inflammatory factors and fibrosis

Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1 ml/kg/day) for 6 weeks.Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-β1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ-induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IκB/NF-κB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation.In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression.     

Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role of oxidative stress in diabetic cardiomyopathy

Long-standing diabetes is associated with increased oxidative stress and cardiac fibrosis. This, in turn, contributes to the progression of cardiomyopathy. The present study was sought to investigate whether the free radical scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) can protect against diabetic cardiomyopathy and to explore the specific underlying mechanism(s) in this setting. Diabetes was induced in rats by a single intraperitoneal injection dose of streptozotocin (50 mg/kg). These animals were treated with tempol (18 mg kg^?1 day^?1, orally) for 8 weeks. Our results showed significant increases in collagen IV and fibronectin protein levels and a marked decrease in matrix metalloproteinase-2 (MMP-2) activity measured by gelatin-gel zymography alongside elevated cardiac transforming growth factor (TGF)-β level determined using ELISA or immunohistochemistry in cardiac tissues of diabetic rats compared with control. This was accompanied by an increased in the oxidative stress as evidenced by increased reactive oxygen species (ROS) production and decreased antioxidant enzyme capacity along with elevated lactate dehydrogenase (LDH) and creatine kinase (CK-MB) serum levels as compared with the control. Tempol treatment significantly corrected the changes in the cardiac extracellular matrix, TGF-β, ROS or serum LDH, CK-MB levels, and normalized MMP-2 activity along with preservation of cardiac tissues integrity of diabetic rats against damaging responses. Moreover, tempol normalized the elevated systolic blood pressure and improved some cardiac functions in diabetic rats. Collectively, our data suggest a potential protective role of tempol against diabetes-associated cardiac fibrosis in rats via reducing oxidative stress and extracellular matrix remodeling.     

Diallyl disulfide ameliorates gentamicin-induced oxidative stress and nephropathy in rats

Experimental evidences suggest a role of reactive oxygen species in gentamicin-induced nephropathy in rats. Therefore, we investigated if diallyl disulfide, a garlic-derived compound with antioxidant properties, has a renoprotective effect in this experimental model. Four groups of rats were studied: (1) control, (2) gentamicin treated subcutaneously with gentamicin (70 mg/kg/12 h/4 days), (3) diallyl disulfide treated intragastrically with diallyl disulfide (50 mg/kg/24 h/4 days), and (4) gentamicin + diallyl disulfide treated with gentamicin + diallyl disulfide. Gentamicin induced (a) nephrotoxicity, (b) increase in renal oxidative stress, and (c) decrease in the activity of manganese superoxide dismutase, glutathione peroxidase, and glutathione reductase. Diallyl disulfide ameliorated these changes induced by gentamicin. The mechanism by which diallyl disulfide has a renoprotective effect in gentamicin-induced acute renal failure in rats may be related, at least in part, to the amelioration in the oxidative stress and the preservation in the activity of the antioxidant enzymes in kidney.     

Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats

The present study was designed to investigate the beneficial role of diosgenin on oxidative stress markers and histopathological changes in aorta of streptozotocin induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal injection of streptozotocin (55mg/kg body weight (b.w.)). From the sixth week, experimental rats received diosgenin at different doses (10, 20 and 40mg/kg b.w.) once daily for 4 weeks. At the end of the experimental periods, diabetic rats exhibited significant increase in the levels of plasma glucose, glycosylated hemoglobin with significant decrease in insulin and total hemoglobin. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and the levels of reduced glutathione were decreased while increases in the levels of lipid peroxidation markers were observed in aortic tissues of diabetic rats. Oral administration of diosgenin to diabetic rats significantly decreased the plasma glucose and increased the insulin level based on a dose dependent manner. Diosgenin at a dose of 40mg/kg b.w. was more pronounced effect than the other two doses and used for further studies. All the manifestations observed in diabetic rats were significantly reversed to near normal at a dose of 40mg/kg b.w. of diosgenin. These findings suggest that diosgenin could have a beneficial role against aortic damage induced by oxidative stress in diabetic state, which was evidenced by the propensity of diosgenin to modulate the antioxidant defense and to decrease the lipid peroxidation in aorta.     

淫羊藿苷对STZ诱导的糖尿病肾病大鼠肾动脉舒缩功能影响的研究

目的：探讨淫羊藿苷（ICA）对链脲佐菌素（STZ）诱导的糖尿病肾病大鼠肾动脉舒缩功能的影响。方法：雄性SD大鼠腹腔注射STZ诱导糖尿病,4周后形成糖尿病肾病模型;随机分为模型组、ICA低、中、高剂量组（30、60、120 mg·kg-1）,灌胃给药;另设正常对照组;疗程9周。取各组大鼠肾动脉制成肾动脉环,比较各组乙酰胆碱（ACh）诱导的舒张作用,并进行体外给药,探究其舒张血管作用的机制。结果：糖尿病肾病大鼠给予ICA能增强ACh诱导的肾动脉舒张效应,能剂量依赖性地舒张内皮完整的肾动脉,L-硝基精氨酸（NLA）能减弱其舒张血管效应。结论：ICA能改善糖尿病肾病大鼠肾动脉舒缩功能,其机制可能与内皮和NO有关。     

Activation of GPR120 in podocytes ameliorates kidney fibrosis and inflammation in diabetic nephropathy

Diabetic nephropathy(DN)is one of the most common causes of end-stage renal disease worldwide.ω3-Fatty acids(ω3FAs)were found to attenuate kidney inflammation,glomerulosclerosis,and albuminuria in experimental and clinical studies of DN.As G protein-coupled receptor 120(GPR120)was firstly identified as the receptor ofω3FAs,we here investigated the function of GPR120 in DN.We first examined the renal biopsies of DN patients,and found that GPR120 expression was negatively correlated with the progression of DN.Immunofluorescence staining analysis revealed that GPR120 protein was mainly located in the podocytes of the glomerulus.A potent and selective GPR120 agonist TUG-891(35 mg·kg^?1·d^?1,ig)was administered to db/db mice for 4 weeks.We showed that TUG-891 administration significantly improved urinary albumin excretion,protected against podocyte injury,and reduced collagen deposition in the glomerulus.In db/db mice,TUG-891 administration significantly inhibited the mRNA and protein expression of fibronectin,collagen IV,α-SMA,TGF-β1,and IL-6,and downregulated the phosphorylation of Smad3 and STAT3 to alleviate glomerulosclerosis.Similar results were observed in high-glucose-treated MPC5 podocytes in the presence of TUG-891(10μM).Furthermore,we showed that TUG-891 effectively upregulated GPR120 expression,and suppressed TAK1-binding protein-1 expression as well as the phosphorylation of TAK1,IKKβ,NF-κB p65,JNK,and p38 MAPK in db/db mice and high-glucose-treated MPC5 podocytes.Knockdown of GPR120 in MPC5 podocytes caused the opposite effects of TUG-891.In summary,our results highlight that activation of GPR120 in podocytes ameliorates renal inflammation and fibrosis to protect against DN.     

Betulinic acid ameliorates endothelium-dependent relaxation in L-NAME-induced hypertensive rats by reducing oxidative stress

Zizyphi Spinosi semen (ZSS) is one of the most widely used traditional Chinese herbs with protective effects on the cardiovascular system. It is not clear whether betulinic acid (BA), the key active constituent of ZSS, has beneficial cardiovascular effects on N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. The objective of this study was to investigate the effect of BA on endothelium-dependent vasorelaxation in isolated aortic rings from L-NAME-induced hypertensive rats and its underlying mechanisms. Male Sprague-Dawley rats were injected with L-NAME (15 mg/kg/d, i.p.) for 4 weeks to induce hypertension. After treatment with L-NAME for 2 weeks, rats with mean blood pressure >120 mm Hg measured by tail-cuff method were considered hypertensive and then injected with BA (0.8, 4, 20 mg/kg/d, i.p.) for the last 2 weeks. The effect of BA on the tension of rat thoracic aortic rings was measured in an organ bath system. The levels of nitric oxide (NO), reactive oxygen species (ROS), and the activity of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in aortas were assayed. We found that BA (0.1-100 μM) evoked a concentration-dependent vasorelaxation in endothelium-intact normal rat aortic rings, which was significantly attenuated by pretreatment with L-NAME (100 μM) or methylene blue (MB, 10 μM), but not by indomethacin (10 μM). Pretreatment with EC(50) (1.67 μM) concentration of BA enhanced the acetylcholine (ACh)-induced vasorelaxation, which was also markedly reversed by both L-NAME and MB. The blood pressure in hypertensive rats increased to 135.22±5.38 mm Hg (P<0.01 vs. control group), which was markedly attenuated by high dose of BA. The ACh-induced vasorelaxation in hypertensive rat aortic rings was impaired, which was markedly improved by chronic treatment with BA (20 mg/kg/d) for 2 weeks. The increase of ROS level and the decrease of NO level, SOD and eNOS activities in hypertensive rat aortas were all markedly inhibited by BA. These results indicate that BA decreased blood pressure and improved ACh-induced endothelium-dependent vasorelaxation in L-NAME-induced hypertension rats, which may be mediated by reducing oxidative stress and retaining the bioavailability of NO in the cardiovascular system.     

黄连素对糖尿病肾损伤大鼠肾功能、氧化应激、肾脏醛糖还原酶的影响

目的观察黄连素对链脲佐菌素诱导的糖尿病肾损伤大鼠肾功能保护作用,并从抗氧化应激、抑制肾脏醛糖还原酶活性及其基因表达等方面探讨黄连素抗糖尿病大鼠肾损伤的作用机制。方法用腹腔注射链脲佐菌素方法复制糖尿病大鼠肾损伤模型。随机分为正常对照组、模型对照组、黄连素组,每组10只。黄连素经口灌胃200 mg.kg-1.d-1,每周给药6 d,共12 wk。比较各组大鼠血糖、肾脏肥大指数(肾重/体重)、尿素氮(BUN)、血肌酐(Cr)、24h尿蛋白(UP24)等肾功能相关指标,比较各组血清超氧化物歧化酶(SOD)活性、脂质过氧化代谢产物丙二醛(MDA)含量、肾组织醛糖还原酶(AR)活性及其基因表达的改变。结果模型组大鼠血糖维持在较高水平、肾脏肥大指数、BUN、Cr、UP24等较正常组明显升高(P<0.05),血清SOD活性低下,MDA含量增加(P<0.05),肾脏AR活性与其基因表达明显升高(P<0.05)。黄连素组与模型组相比,能明显降低血糖、有效控制体重下降、明显改善肾脏肥大指数、BUN、Cr、UP24等指标(P<0.05),血清SOD活性增强,同时MDA含量减少(P<0.05),肾脏AR活性降低及AR mRNA水平下调(P<0.05)。结论对糖尿病肾损伤大鼠,黄连素在调节血糖的同时,可能通过提高机体抗氧化能力、减少肾脏AR活性与基因表达以抑制多元醇通路的激活发挥其肾功能的保护作用。     

Thymoquinone ameliorates renal oxidative damage and proliferative response induced by mercuric chloride in rats

We tested the hypothesis if thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone) could ameliorate renal oxidative damage and proliferative response induced by mercuric chloride (HgCl2) in rats. HgCl2 (3 mg/kg) was administered subcutaneously to each one of two groups of rats: (i) HgCl2-thymoquinone group that received thymoquinone (10 mg/kg/day); and (ii) HgCl2 group that received vehicle instead of thymoquinone. A third group of rats was reserved as control group. Rats were killed 24, 48 and 72 hr after HgCl2 administration for histological and biochemical studies. Our findings show that treatment with thymoquinone offers imperative protection from HgCl2-induced nephrotoxicity. The deterioration of antioxidant enzymes, increment of serum creatinine and histological damage caused by HgCl2 are markedly improved by thymoquinone treatment. Apoptosis and proliferative reactions are also reduced. The maximal protection offered by thymoquinone treatment was particularly noticeable 48 and 72 hr after administration of the toxic agent at the time when histological damage, renal cell apoptosis and proliferative reactions reached their maximum. These observations may be attributed partially to the antioxidant effect of thymoquinone and suggest that it may be a clinically valuable agent in the prevention of acute renal failure caused by inorganic mercury intoxication.     

Total flavonoids of Epimedium ameliorates testicular damage in streptozotocin‐induced diabetic rats by suppressing inflammation and oxidative stress

Testicular damage is the anomaly that will often accompany diabetes mellitus. Thus, this study aimed to investigate the role that total flavonoids of Epimedium (TFE) played against streptozotocin (STZ)‐induced diabetic testicular dysfunction and to elucidate the mechanism of action. The diabetic rat model was induced by vein injection of STZ in healthy rats. Thirty male healthy Spraque‐Dawley rats were randomly divided into following groups: the control group, the diabetic group, and the diabetic + TFE group. Gastrointestinal administration begins at fifth week of TFE for 6 weeks. After TFE administration, all animals were euthanized. Testicular tissue samples and blood samples of rats were collected for histopathological examination and for determination of levels of various biomarkers including blood glucose, testosterone, testicular enzymes, and oxidative stress indicators. All testes were weighted to calculate the testicular organ index. Hematoxylin‐eosin staining was used for observing the testis and epididymis pathological changes. Protein expression (monocyte chemoattractant protein‐1, transforming growth factor‐beta‐1, interleukin‐6, and 3‐beta‐hydroxysteroid dehydrogenase) was detected by immunohistochemistry and western blot techniques. There was a significant difference in the changes between the diabetes group and the control group. As a result of treat with TFE, the blood glucose decreased but there was no significant difference, and other indicators showed significant improvement. TFE may protect against STZ‐induced testicular injury by suppressing inflammation and oxidative stress.     

Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats

5-Fluorouracil (5-FU) is a potent antineoplastic agent commonly used for the treatment of various malignancies. It has diverse adverse effects such as cardiotoxicity, nephrotoxicity and hepatotoxicity which restrict its wide and extensive clinical usage. It causes marked organ toxicity coupled with increased oxidative stress and apoptosis. Chrysin (CH), a natural flavonoid found in many plant extracts, propolis, blue passion flower. It has antioxidative and anti-cancerous properties. The present study was designed to investigate the protective effects of CH against 5-FU induced renal toxicity in wistar rats using biochemical, histopathological and immunohistochemical approaches.Rats were subjected to prophylactic oral treatment of CH (50 and 100 mg/kg b.wt.) for 21 days against renal toxicity induced by single intraperitoneal administration of 5-FU (150 mg/kg b.wt.). The possible mechanism of 5-FU induced renal toxicity is the induction of oxidative stress; activation of apoptotic pathway by upregulation of p53, bax, caspase-3 and down regulating Bcl-2. However prophylactic treatment of CH decreased serum toxicity markers, increased anti-oxidant armory as well as regulated apoptosis in kidney. Histopathological changes further confirmed the biochemical and immunohistochemical results. Therefore, results of the present finding suggest that CH may be a useful modulator in mitigating 5-FU induced renal toxicity.     

缬沙坦对糖尿病肾病大鼠肾脏氧化应激的影响

目的观察缬沙坦干预治疗后糖尿病大鼠肾脏氧化应激的变化,探讨缬沙坦保护肾脏的部分机制。方法以链脲佐菌素建立糖尿病大鼠模型,缬沙坦干预治疗10周,观察大鼠糖代谢、肾功能及肾皮质内丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。结果糖尿病大鼠糖化血红蛋白、血尿素氮、24h尿总蛋白、尿白蛋白定量(24h)、24h尿量、肾皮质MDA含量显著升高;肾皮质SOD活性显著降低。缬沙坦干预治疗组上述指标改善,差异有统计学意义。结论氧化应激参与了糖尿病肾病(DN)的发病过程,缬沙坦对DN的治疗作用部分是通过抗氧化实现的。     

Cephaloridine nephrotoxicity in streptozotocin induced diabetic Fischer 344 (F344) rats

The purpose of this study was to determine if cephaloridine nephrotoxicity is attenuated in streptozotocin (STZ)-induced diabetic rats. Fischer 344 (F344) rats (205-250 g) were given a single injection (i.p.) of STZ (27-35 mg/kg) or citrate buffer. The nephrotoxicity of (750 mg/kg) cephaloridine (i.p.) was then compared with normoglycemic and 14-day diabetic rats. Increased blood urea nitrogen (BUN) levels as well as diminished renal cortical slice accumulation of tetraethylammonium (TEA) and lactate-stimulated p-aminohippurate (PAH) were measured (P less than 0.05) in normoglycemic rats 48 h after cephaloridine administration. Cephaloridine failed to alter BUN levels and organic ion accumulation in diabetic rats. Diabetes did not totally protect against cephaloridine toxicity since kidney weights were elevated in normoglycemic and diabetic rats 48 h after administration of 750 mg/kg cephaloridine. A series of experiments also measured BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA 24, 48 and 72 h after (1500 mg/kg) cephaloridine administration. Cephaloridine increased (P less than 0.05) kidney wt and decreased PAH and TEA uptake (P less than 0.05) in the normoglycemic group at 24-72 h. No change in kidney wt, PAH or TEA uptake was observed in the diabetic rats. These data indicate diabetes reduces cephaloridine nephrotoxicity.     

红景天苷对链脲佐菌素所致糖尿病大鼠肝脏的保护作用

目的研究红景天苷对链脲佐菌素所致糖尿病大鼠肝脏的保护作用.方法一次性ip链脲佐菌素(60 mg/kg)制备糖尿病大鼠模型,取造模成功的糖尿病大鼠80只,按血糖水平随机分为模型组,红景天苷25、50、100 mg/kg组以及盐酸二甲双胍(25 mg/kg)组,每组16只;另取同龄正常饲养大鼠16只作为对照组.ip给药治疗,1次/d,疗程为12周.分别于0、4、8、12周测定各组大鼠血糖水平.治疗12周后,测定各组大鼠体质量和肝脏指数;检测血清中转氨酶(ALT、AST)、碱性磷酸酶(ALP)活性;测定肝脏组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量;并通过HE染色观察肝脏组织病理学改变.结果与模型组比较,红景天苷50、100 mg/kg组大鼠血糖水平显著降低(P<0.05、0.01),肝脏指数显著降低、体质量显著增高(P<0.05、0.01),血清中ALP活性明显降低(P<0.01),肝脏组织中SOD、CAT活性显著升高(P<0.05、0.01);红景天苷25、50、100 mg/kg组大鼠血清中转氨酶(ALT、AST)活性和肝组织中MDA含量显著降低(P<0.05、0.01);红景天苷组大鼠肝组织病理形态学改变程度明显减轻.结论 红景天苷对链脲佐菌素所致糖尿病大鼠肝脏具有剂量相关性的保护作用,其作用机制可能与红景天苷能够有效改善抗氧化酶系统活性、降低氧化应激损伤,从而改善肝功能有关.     

益气养肾方对糖尿病肾病大鼠氧化应激的影响观察

目的：观察益气养肾方对糖尿病肾病大鼠应激反应水平的影响。方法选择10周龄SD大鼠50只,选取其中10只作为对照组,给予常规低脂、低糖饮食。其余40只采用高脂、高糖喂养联合低剂量（30mg/kg）链脲佐菌素诱导糖尿病肾病大鼠动物模型。建模成功后随机分为模型组与观察组各20只。观察组在模型组饮食基础上将药物益气养肾方按人与大鼠体表面积折算动物等效药量,按生药20g·kg-1·d-1,灌胃,连续灌胃3周。模型组同期继续给予高脂、高糖饮食。3周后杀死大鼠,手术摘取肾脏。病理切片观察3组肾脏组织形态学变化,比较3组大鼠肾脏肥大指数（ kW/BW）、尿蛋白排泄量（24hUP）、血肌酐（ Scr）水平、肾皮质丙二醛（ MDA）含量、肾皮质超氧化物歧化酶（SOD）活性、肾皮质谷胱甘肽过氧化物酶（GSH-Px）。结果3组大鼠光镜下观察：对照组大鼠肾小球及肾小管正常,基底膜及系膜区结构清楚。模型组大鼠HE染色见肾小球肥大,肾小球毛细血管基底膜不规则增厚,肾小管上皮细胞肥大,内有糖原沉积表现,肾小管间纤维变性。观察组光镜观察可见与模型组相似病理改变,但肾小球肥大及肾小管肿胀较轻,蛋白管型较少。模型组及观察组kW/BW、24hUP、Scr较对照组明显升高,差异均有统计学意义（P＜0.05）,但观察组kW/BW、24hUP、Scr较模型组明显减少,差异均有统计学意义（ P＜0.05）。模型组及观察组MDA含量明显升高,SOD及GSH-Px较对照组明显降低,差异均有统计学意义（ P＜0.05）。观察组MDA含量较模型组明显减少,SOD、GSH-Px较模型组明显增加,差异均有统计学意义（ P＜0.05）。结论益气养肾方可能通过抑制糖尿病肾病大鼠体内氧化应激反应来减轻肾脏损伤,改善糖尿病肾病大鼠肾脏结构及起到功能保护作用。