Effects of Heparin on Transforming Growth Factor-β_1 and Extracellular Matrix Components in the Glomeruli of Diabetic Rats

The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.

Association of Chinese Medicine Constitution Susceptibility to Diabetic Nephropathy and Transforming Growth Factor-β1(T869C)Gene Polymorphism

Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP） was screened for 180 DN cases and 180 type 2 diabetic mellitus（T2DM） cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire （CCMQ）.Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1（T869C） gene polymorphisms.Results：The DN group has a higher frequency of TGF-β1（T869C） gene polymorphism than the T2DM group,and CC/CT genotypes than the T2DM group[CC,CT,TT（DN group）：88,87,5（cases） versus（T2DM group） 71,73,36（cases）,P0.05].The phlegm-dampness constitution,damp-heat constitution,and blood stasis constitution have correlations with TGF-β1 （T869C） gene polymorphism.Conclusion：Chinese medicine constitutions were associated with TGF-β1（T869C） gene polymorphism,a potential predictor of susceptibility to DN in T2DM patients.

Effect of Ethanol Extract of Rhodiola Rosea on the Early Nephropathy in Type 2 Diabetic Rats

Summary： This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy （DN）. The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin （STZ）. Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Cap- topril group. Oral glucose tolerance test （OGTT） was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose （FBG）, total cholesterol （TC）, triglyceride （TG）, creatinine clearance rate （Ccr）, 24-h urinary albumin （UA）, the ratio of kidney mass/body weight （renal index） and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor （TGF）-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of con- trol group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.

Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats

Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.

Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy

Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.

Serum expression and clinical significance of miR-342-5p and miR-423-5p in type 2 diabetes mellitus patients with different urinary albumin excretion rate

Objective:To study the serum expression and clinical significance of miR-342-5p and miR-423-5p in type 2 diabetes mellitus patients with different urinary albumin excretion rate. Methods: A total of 126 patients with type 2 diabetes mellitus treated in our hospital between May 2013 and December 2015 were selected and divided into normal urine protein group (NA group), micro-urine protein group (MI group) and macro-urine protein group (MA group) according to the urinary albumin/creatinine ratio (ACR);50 healthy volunteers were selected as control group. Serum was collected to determine the expression miR-342-5p and miR-423-5p as well as the content of p38MAPK and TGF-毬1 signaling pathway molecules.Results:Serum miR-342-5p and miR-423-5p expression of NA group, MI group and MA group were significantly higher than those of control group and the higher the ACR, the higher the serum miR-342-5p and miR-423-5p expression;serum MAPKKK, p38MAPK, CREB, ATF-2, TGF-毬1, Smad2, Smad3, Smad4 and CTGF content of patients with high miR-342-5p and miR-423-5p expression were significantly higher than those of patients with low miR-342-5p and miR-423-5p expression.Conclusions: Highly expressed miR-342-5p and miR-423-5p in patients with type 2 diabetes mellitus can be targeted to adjust p38MAPK and TGF-毬1 signaling pathway to cause the occurrence of diabetic nephropathy.