ABSTRACT
<p><b>OBJECTIVE</b>To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose.</p><p><b>METHODS</b>Healthy SD rats were randomly divided into 3 groups: normal control group (A), stable high blood glucose group (B) and fluctuant high blood glucose group (C). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The superoxide dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry. The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western blot. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL).</p><p><b>RESULTS</b>After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group.</p><p><b>CONCLUSION</b>Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Blood Glucose , Metabolism , Diabetes Mellitus, Experimental , Metabolism , Pathology , Epithelial Cells , Metabolism , Kidney Tubules , Cell Biology , MAP Kinase Kinase 4 , Metabolism , MAP Kinase Signaling System , Malondialdehyde , Metabolism , NADPH Oxidase 4 , NADPH Oxidases , Metabolism , Rats, Sprague-Dawley , Superoxide Dismutase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between type 2 diabetes mellitus (T2DM) and the mutations in the fragment of mitochondrial DNA (mtDNA) from nucleotides 3153 to 3551, which have shown high frequency of point mutation.</p><p><b>METHODS</b>One hundred and ninety-one normal controls and 222 patients with T2DM were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), T-A cloning sequencing and denatured high performance liquid chromatography (DHPLC) techniques.</p><p><b>RESULTS</b>The prevalence of mtDNA mutations in the patient group (24.32%) was significantly higher than that in the control group (7.33%) (P < 0.05). Three novel mutations of A3209T, T3253G and A3467C were found, and C3497T was first reported in DM. Onset age, body mass index, fasting blood glucose, HbA1C, high density lipoprotein-cholesterol and diabetic nephropathy could be related to occurrence of mtDNA mutations (P < 0.05).</p><p><b>CONCLUSION</b>Mitochondrial DNA mutations might implicate T2DM in Wenzhou population, which should play an important role in the pathogenesis of T2DM.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Chromatography, High Pressure Liquid , DNA Mutational Analysis , DNA, Mitochondrial , Genetics , Diabetes Mellitus, Type 2 , Genetics , Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
Diabetic rats were induced by intraperitoneal injection of streptozotocin.TUNEL and immunohistochemistry results showed that the renal tubular cell apoptosis index(AI)and Bax protein expression were significantly reduced,and the Bcl-2 protein expression in glomeruli was significantly increased in diabetic rats with stable hyperglycemia treated by benazepril compared with diabetic rats with stable hyperglycemia treated by vehicle(all P