Regulation of C-type natriuretic peptides and natriuretic peptide receptor-B expression in diabetic rats renal treated by Tongluo Recipe / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of C-type natriuretic peptides (CNP) and natriuretic peptide receptor-B (NPR-B) receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe (TLR).</p><p><b>METHODS</b>Sixty male SD rats were divided into 3 groups: the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin (STZ)-induced diabetic rats were treated with TLR (1.0 g·kg(-1)·d(-1)) for 4 and 12 weeks, respectively. (1) The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. (2) CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction (PCR) on rats renal cortex. (3) Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay (ELISA). (4) Pathological evaluation and NPR-B immunostaining for renal tissue were also performed.</p><p><b>RESULTS</b>(1) CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. (2) Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. (3) Renal lesions like glomerular volume increased are observed mostly in the relative early stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement.</p><p><b>CONCLUSION</b>CNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.</p>

Sulodexide prevents diabetic nephropathy through inhibiting renal NF-κB activation and MCP-1 expression / 中华肾脏病杂志

Objective To study the effects of sulodexide on renal NF-κB activation and monocyte chemotactic protein 1 (MCP-1) expression in diabetic rats and elucidate the possible mechanism of sulodexide in preventing diabetic nephropathy (DN). Methods Wistar rats were fed with high-sucrose-high-fat diet and injected with a low dose of STZ (streptozotocin,35 mg/kg) into abdominal cavity to induce diabetes.DM rats were randomly divided into non-treated group of treatment,blood glucose (BG),triglyceride (TG),cholesterol,serum creatinine (Scr),urea nitrogen (BUN),24 h urinary albumin excretion (UAE) were measured.HE staining was performed in renal tissues for light microscopy examination of mean glomerular volume (MGV).MCP-1 expression was detected by immunohistochemical method.NF-κB activation was determined by Western blot. Results Compared with NC group,DM group and DMS group had significant elevated BG,TG and TC levels (all P＜0.01).There were no significant differences of BG,TG or TC levels between DM group and DMS group.Compared with NC group,DM group and DMS group had significant increased Scr,BUN,UAE levels (all P＜0.01).Scr,BUN,UAE levels were significantly lower in DMS group than those in DM group [(39.1±0.88) μmol/L vs (41.0±2.16) μmol/L,(9.12±1.06) mmol/L vs (9.87±0.19) mmol/L； (19.92±0.96) mg/24 h vs (25.99±0.52)mg/24 h,all P＜0.05].Compared with NC group,the MGV of DM group was significantly increased [(7.47±1.11)×105 μm3 vs (4.22±1.09)×105 μm3,P＜0.01].Compared with DM group,the MGA of DMS group was significantly reduced [(6.64±0.71)×105 μm3 vs (7.47±1.11)×105 μm3,P＜0.05],but was still increased compared with that of NC group (P＜0.01).Compared with NC group,the MCP-1 expression of DM group was significantly higher [(12.17±1.94)/HPF vs (1.19±0.70)/HPF,P＜0.01].MCP-1 expression in DSM group was significantly lower than that of DM group [(9.22± 1.61)/HPF vs (12.17±1.94)/HPF,P＜0.01],but still higher than that of control group (P＜0.01).Compared with NC group,the NF-κB activity was significantly higher in DM group [(0.89±0.07) vs (0.24±0.03),P＜0.01].Compared with DM group,NF-κB activity of DMS group was significantly lower [(0.27±0.01) vs (0.89±0.07),P＜0.01].There was no significant difference of NF-κB activity between DMS group and NC group. Conclusion Sulodexide has protective effects on diabetic nephropathy,and one of the mechanisms may involve the inhibition of NF-κB activation as well as the suppression of MCP-I expression.

Study on mitochondrial DNA gene tRNA(Leu(UUR)) A3243G mutation in type 2 diabetes mellitus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the prevalence and the clinical characteristics of mitochondrial gene mutation A3243G (mt tRNA(Leu(UUR)) 3243 A-->G) in patients with type 2 diabetes mellitus (DM2) in China.</p><p><b>METHODS</b>Four hundred and twenty-eight cases of DM2 patients were selected randomly. One hundred and eighty-eight individuals were healthy controls. The mutation was assayed by PCR-restriction fragment length polymorphism technique. The target fragments of PCR were digested with restriction endonuclease Apa I.</p><p><b>RESULTS</b>mt tRNA(Leu(UUR)) 3243A-->G gene mutation was found in 2 of 428 patients with DM2, but not found in the controls. Further investigation of the relatives of the 2 patients' families revealed that 3 members were the carriers of mt tRNA A3243G gene mutation and the patients with diabetes. In addition, one proband and her son were characterized with the syndrome of mitochondrial encephalomyopathy with lactic acidosis. The diabetes of these patients is frequently accompanied by hearing impairment or deafness with maternal inheritance.</p><p><b>CONCLUSION</b>The prevalence of the mitochondrial gene A3243G mutation is 0.47% in DM2 patients in China. The data acquired in this study suggest that the clinical phenotype of these patients with A3243G should be heterogeneous.</p>