Tropisetron ameliorates early diabetic nephropathy in streptozotocin‐induced diabetic rats

It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti‐inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin‐induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor‐α were also determined. Streptozotocin‐treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor‐α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor‐α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti‐oxidative and anti‐inflammatory mechanisms that appear to be independent of the 5‐HT₃ receptor.     

Lithospermic acid B ameliorates the development of diabetic nephropathy in OLETF rats

Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal models. In the present study we investigated the effects of LAB on the prevention of diabetic nephropathy in type 2 diabetic Otsuka Long-Evans-Tokushima Fatty (OLETF) rats. LAB (20 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. Treatment of OLETF rats with LAB had little effects on body weight and blood glucose levels. Treatment with LAB resulted in significant reduction in blood pressure. LAB markedly attenuated albuminuria and significantly lowered levels of lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-beta1) expression in renal tissues of OLETF rats. In addition, LAB inhibited the progression of glomerular hypertrophy, mesangial expansion, and expansion of the extracellular matrix in the renal cortex. Collectively, these results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing blood pressure, oxidative stress, and MCP-1 expression. Our results suggest that LAB might be a new therapeutic agent for the prevention of nephropathy in type 2 diabetes.     

N-hexacosanol ameliorates streptozotocin-induced diabetic rat nephropathy

In this study we investigated the effects of N-hexacosanol on streptozotocin-induced rat diabetic nephropathy. Diabetes was induced in 8-week-old male Sprague-Dawley rats by administering an intraperitoneal injection of streptozotocin (50 mg/kg). The rats were divided into four groups and maintained for 8 weeks: control rats, diabetic rats without treatment with N-hexacosanol, and diabetic rats treated with N-hexacosanol (2 mg/kg and 8 mg/kg i.p. every day). Although N-hexacosanol failed to modify the diabetic status, increases in serum creatinine as well as in kidney weight were significantly reduced. The malonaldehyde and transforming growth factor beta-1 (TGF-beta1) concentrations as well as the protein kinase C (PKC) activities in the diabetic kidney were significantly higher than those of the control, which were decreased by treatment with N-hexacosanol. Histological examinations revealed that N-hexacosanol significantly ameliorated diabetic-induced tubulointerstitial pathological changes. Our data suggest that N-hexacosanol could prevent increases in the malonaldehyde and TGF-beta1 concentrations and PKC activities in the kidney, and ameliorate diabetic-induced nephropathy.     

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.     

Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy

Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy(DN),and tubular epithelial cells(TECs)are crucial promoters o...     

Urocortin ameliorates diabetic nephropathy in obese db/db mice

BACKGROUND AND PURPOSE: Hyperglycaemia induces overproduction of mitochondrial reactive oxygen species (ROS) in endothelial cells, which is believed to be a major molecular mechanism underlying complications of diabetes, including diabetic nephropathy. Impairment of endothelium-dependent vasodilatation is found in type 2 diabetes. Urocortin is a 40 amino-acid peptide related to the corticotrophin-releasing factor (CRF) family, which suppresses production of ROS in endothelial cells and sustains endothelium-dependent relaxations of rat coronary artery. However, it is not clear if urocortin has any effect on diabetic nephropathy. EXPERIMENTAL APPROACH: Possible mechanisms underlying the effects of urocortin on diabetic nephropathy were investigated in db/db mice and cultured rat mesangial cells. KEY RESULTS: Urocortin decreased body weight, plasma levels of advanced glycation end-products, blood urea nitrogen and creatinine levels. However, food intake, plasma insulin and glucose levels remained unaffected. Superoxide dismutase activity was increased markedly, whereas malonaldehyde levels in kidney homogenate and sorbitol concentrations in red blood cells were decreased significantly in urocortin-treated mice. Urocortin significantly decreased glomerular extracellular matrix expansion and accumulation in kidney. Moreover, urocortin inhibited the overexpression of transforming growth factor-beta 1 and connective tissue growth factor in rat mesangial cells induced by 25 mM glucose. All the effects of urocortin, except sorbitol accumulation, were abolished by the non-selective CRF receptor blocker, astressin. CONCLUSION AND IMPLICATIONS: Urocortin could significantly ameliorate diabetic nephropathy and this effect was mediated via the CRF receptor.     

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats

Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.     

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.     

Astilbin attenuates hyperuricemia and ameliorates nephropathy in fructose-induced hyperuricemic rats

Astilbin is a flavonoid compound isolated from the rhizome of Smilax china L. The effects and possible mechanisms of astilbin on hyperuricemia and nephropathy rats were elucidated in this study. Different dosages of astilbin (1.25, 2.5, and 5.0 mg/kg) were administered to 10?% fructose-induced hyperuricemic rats. The results demonstrated that astilbin significantly decreased the serum uric acid (Sur) level by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) but not inhibiting the xanthine oxidase (XOD) activity. In addition, kidney function parameters such as serum creatinine (Scr) and blood urea nitrogen (BUN) were recovered in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of transforming growth factor- β1 (TGF-β1) and connective tissue growth factor (CTGF) and also exerted a renal protective role by inhibiting formation of monosodium urate (MSU) and production of prostaglandin E? (PGE?) and interleukin-1 (IL-1). These findings provide potent evidence for astilbin as a safe and promising lead compound in the development of a disease-modifying drug to prevent hyperuricemia and nephropathy.     

Carvedilol ameliorates endothelial dysfunction in streptozotocin-induced diabetic rats

The beta-blocker, carvedilol has an additional endothelium-dependent vasodilating properties in patients with hypertension or heart failure. Whether carvedilol can improve endothelium-dependent relaxation in a diabetic animal model and its mechanism of action are unknown. The aim of this study was to investigate the effect of carvedilol on the endothelial-response of aortas from diabetic rats and the underlying mechanism. Acetylcholine-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, and expression of nitric oxide synthase 3 (NOS3) mRNA were measured in aortas isolated from both non-diabetic and streptozotocin-induced diabetic rats. The level of NO in serum was also measured 5 weeks after carvedilol administration (1 or 10 mg/kg/day). Endothelium-dependent relaxation declined along with the decrease of serum NO level in aortas from diabetic rats. Treatment with carvedilol for 5 weeks prevented the inhibition of endothelium-dependent relaxation and the decrease of serum NO levels caused by diabetes. The expression of NOS3 mRNA, protein expression and NOS3 phosphorylation at Ser1177 in diabetic rat aorta was very low in untreated diabetic aortas compared with the healthy group. Administration of carvedilol not only significantly increased the expression of NOS3 mRNA but also protein expression and NOS3 phosphorylation at Ser1177 in the healthy and diabetic groups. In conclusion, chronic carvedilol administration significantly ameliorated the endothelial dysfunction in diabetic rat aortas, in which increased NO level, up-regulated NOS3 mRNA and phosphorylation at Ser1177 may be involved.     

Lycopene ameliorates erectile dysfunction in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is characterized by oxidative stress, which is one of the major pathophysiological mechanisms underlying diabetic erectile dysfunction (ED). Lycopene is one of the most potent antioxidants among the natural carotenoids. The present study was aimed to investigate whether lycopene could lower oxidative stress and attenuate ED in diabetic rats. Lycopene (10, 30, 60 mg/kg/d) was administered via intragastric intubation for 8 weeks to streptozotocin (STZ) (50 mg/kg, i.v.) induced diabetic rats. The results showed that chronic lycopene treatment significantly and dose dependently restored ED in diabetic rats by lowering blood glucose, reducing oxidative stress and up-regulating eNOS expression. These results indicated that lycopene treatment is potentially a new strategy for treating diabetic ED.     

Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy

Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100 mg/kg) for 2 weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-β1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-β1/Smad3 signaling.     

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.     

KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats

1. We examined whether KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)-induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM-1K-SHR) or not. 2. The oral administration of KRH-594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM-1K-SHR. 3. In a histological study, KRH-594 (3 and 10mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently improved glomerulosclerosis and the hyalin cast of tubules in DM-1K-SHR kidneys. Both KRH-594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose-dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM-1K-SHR. 5. These results suggest that KRH-594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.     

NFAT2 inhibitor ameliorates diabetic nephropathy and podocyte injury in db/db mice

BACKGROUND AND PURPOSE

Podocyte injury plays a key role in the development of diabetic nephropathy (DN). We have recently shown that 11R-VIVIT, an inhibitor of cell-permeable nuclear factor of activated T-cells (NFAT), attenuates podocyte apoptosis induced by high glucose in vitro. However, it is not known whether 11R-VIVIT has a protective effect on DN, especially podocyte injury, under in vivo diabetic conditions. Hence, we examined the renoprotective effects of 11R-VIVIT in diabetic db/db mice and the possible mechanisms underlying its protective effects on podocyte injury in vivo and in vitro.

EXPERIMENTAL APPROACH

Type 2 diabetic db/db mice received i.p. injections of 11R-VIVIT (1 mg·kg⁻¹) three times a week and were killed after 8 weeks. Immortalized mouse podocytes were cultured under different experimental conditions.

KEY RESULTS

11R-VIVIT treatment markedly attenuated the albuminuria in diabetic db/db mice and also alleviated mesangial matrix expansion and podocyte injury. However, body weight, food and water intake, and glucose levels were unaffected. It also attenuated the increased NFAT2 activation and enhanced urokinase-type plasminogen activator receptor (uPA receptor) expression in glomerulor podocytes. In cultured podocytes, the increased nuclear accumulation of NFAT2 and uPA receptor expression induced by high glucose treatment was prevented by 11R-VIVIT or NFAT2-knockdown; this was accompanied by improvements in the filtration barrier function of the podocyte monolayer.

CONCLUSIONS AND IMPLICATIONS

The NFAT inhibitor 11R-VIVIT might be a useful therapeutic strategy for protecting podocytes and treating DN. The calcinerin/NFAT2/uPA receptor signalling pathway should be exploited as a therapeutic target for protecting podocytes from injury in DN.     

Salvianolic acid A ameliorates AGEs-induced glomerular endothelial dysfunction and protects against diabetic nephropathy

OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg~(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg~(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg~(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg~(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.     

Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats

Abstract

Context: In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored.

Objective: The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats.

Material and methods: The aqueous suspension of P. dactylifera seeds (aqPDS) (1?g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase.

Results: Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248?±?42 versus 508?±?60?mg/dl), urea (32?±?3.3 versus 48.3?±?5.6?mg/dl), creatinine (2.2?±?0.35 versus 3.8?±?0.37?mg/dl), ALT (29.6?±?3.9 versus 46.4?±?5.9?IU/l), and AST (73.3?±?13 versus 127.8?±?18.7?IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats.

Discussion and conclusion: The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.     

黄蛭合剂治疗糖尿病肾病的临床研究

目的探讨黄蛭合剂应用于糖尿病肾病治疗的临床疗效。方法选取糖尿病肾病患者130例,随机分为有可比性的两组,其中对照组给予基础治疗,观察组在对照组基础上给予黄蛭合剂口服。监测两组患者治疗前后的空腹血糖（FPG）、餐后2h血糖（2hPG）、血肌酐（SCr）、血尿素氮（BUN）、尿蛋白排泄率（UAER）、尿β2微球蛋白（β2-MG）、血清总胆固醇（TC）、血清三酰甘油（TG）。结果两组患者治疗后FPG、2hPG、SCr、BUN、UAER、β2-MG、TC、TG均较治疗前明显改善（P〈0.05）;其中FPG、2hPG、SCr两组改善程度无明显差异（P〉0.05）;BUN、UAER、β2-MG、TC、TG观察组改善程度较对照组更为明显（P〈0.05）。结论给予糖尿病肾病患者黄蛭合剂口服,在有效控制血糖的同时,可以明显改善肾功能,值得临床推广。     

Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

Oxidative stress and apoptotic cell death in kidney have been suggested as contributing factors in the development and complication of diabetes especially in diabetic nephropathy (DN). This study investigated the effects of trigonelline (TG) on the renal functional, morphological changes and renal apoptosis in neonatal diabetic rats, a model of non-insulin-dependent diabetes mellitus. Diabetes mellitus was induced in one day old neonatal Wistar rat pups by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (50 mg/kg) and monitored for 16 weeks thereafter. The diabetic rats were divided as follows: the nSTZ diabetic group, the TG (50 mg/kg) treated diabetic group, and the TG (100 mg/kg) treated diabetic group. The age matched nondiabetic group received an injection of citrate buffer (0.1 M, pH 4.5). At the end kidney samples were taken for light microscopic examinations. The levels of serum creatinine and BUN were significantly low in TG (100 mg/kg) treated diabetic rats. Glomerular filtration rate was improved in TG treated rats. The activities of antioxidant enzyme and membrane bound enzyme were decreased and the levels of tumor necrotic factor (TNF-α) and hydroxyproline content were increased in renal tissues of the diabetic group. TG (100 mg/kg/day) treatment for a period of 4 weeks showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. The degenerative changes in kidney tissue and fibrosis were alleviated in the TG treated groups. These results suggested that TG might have a significant role in alleviating kidney damage in nSTZ-diabetic rats.