| Objective: Type 2 diabetic rats model was established by high-fat and high-sugar dietand intraperitoneal injection of a low dose of streptozotocin (STZ).To observe theexpression of NADPH oxidase subunits p22phox and Nox4 in the heart of type 2diabetic rats. To explore the effect of telmisartan on the expression of NADPHoxidase subunits p22phox and Nox4 in the heart of type 2 diabetic rats.Methods: Thirty-six male Wistar rats were randomly divided into two parts: commongroup (group A, n=10), model group of rats with diabetic (n=26). The rats in Group Awere healthily fed with ordinary diet. The rats in model group were fed withhigh-suger and high-fat diet. After four weeks, the model rats were injected with smalldose of STZ (30mg/kg) by abdominal cavity. At the end of six weeks, detectionfasting blood sugar(FBG), if the rats with FBG≥7.8mmol/L and insulin resistancewere estimated to type 2 diabetic models . There were 20 rats successfully induced tobe diabetic. Model rats with diabetic were randomly divided into diabetic subgroup(group B,n=10) and telmisartan-treated subgroup (group C,n=10). Rats in group Cwere orally administered telmisartan (5mg/kg), and rats in group A and B were givenequivalent volume of normal saline. 12 weeks for intervention, all animals were fastedand banned water for 12h, and the body weight was measured. After anesthetized,blood by abdominal cardinal vein, preparation into plasma specimens. Sample wasrespectively used to measure fasting blood glucose, adiponectin, insulin and bloodlipid. Use formula to compute insulin sensitivity index. Rats after completion of theinspection to be sacrificed, take out the heart from thoracic cavity after the rat wassacrificed immediately. The heart was washed with normal sodium and dried byfilter-paper and then weighed. The partial left ventricle was fixed by formalin,embedded by paraffins and sliced for immunohistochemistry stain to detect theprotein expression of myocardial connective tissue growth factor (CTGF) andcopper-zinc-superoxide dismutase (Cu-Zn-SOD). Another part of left ventricle wasput in the liquid nitrogen until freeze through, and then stockpiled in the -70℃freezerfor real-time fluorescence quantitative polymerase chain reaction (PCR) to detect themRNA expression of myocardial p22phox and Nox4.Results:1. General characteristics. Compared with group A of normal control group, the levels of fasting bloodglucose, plasma insulin, cholesterol and triglyceride were obviously increased indiabetic group B and had higher ratio of heart to body weight. (P＜0.05). The plasmaadiponectin levels and insulin sensitivity index were obviously reduced in group B (P＜0.05). After telmisartan treatment, group C displayed lowered fasting blood glucose,plasma insulin, cholesterol and triglyceride, the ratio of heart to body weight wasdecreased(P＜0.05). But the plasma adiponectin levels and insulin sensitivity indexwere obviously increased in group C than that in group B (P＜0.05).2. The mRNA expression of myocardial Nox4 and p22phox.Compared with group A of normal control group, the mRNA expression ofmyocardial p22phox and Nox4 were obviously increased in group B (P＜0.05). Aftertelmisartan treatment, the mRNA expression of myocardial p22phox and Nox4 weredecreased in group C than those in group B (P＜0.05).3. The protein expression of myocardial CTGFCompared with group A of normal control group, the protein expression ofmyocardial CTGF was obviously increased in group B (P＜0.05) . After telmisartantreatment, the protein expression of myocardial CTGF was decreased in group C thanthose in group B (P＜0.05).4. The protein expression of myocardial Cu-Zn-SODCompared with group A of normal control group, the protein expression ofmyocardial Cu-Zn-SOD was obviously decreased in group B (P＜0.05) . Aftertelmisartan treatment, the protein expression of myocardial Cu-Zn-SOD wasobviously increased in group C than those in group B (P＜0.05).5. The results of the myocardium stained by HEMyocardial fiber lined up in order, and there was no hypertrophy. Cellularnucleus was spherical or ellipse, nucleus was obvious and in cell centers, and therewas no swelling in nucleus in group A. Group B rats: Myocardial fiber lined up indisporder, and was hypertrophy, swelling and fracture. Myocardial cell borders arenot clear. The size of cellular nucleus was irregular. After telmisartan treatment, allthese changes were attenuated in diabetic rats.Conclusions:The ratio of heart to body weight and the mRNA expression of myocardialp22phox and Nox4 were obviously increased, and the protein expression ofmyocardial CTGF was obviously increased, the protein expression of myocardial Cu-Zn-SOD and plasma adiponectin levels were obviously reduced in type 2 diabeticrats. After telmisartan treatment, the ratio of heart to body weight, the mRNAexpression of myocardial p22phox and Nox4 and the protein expression ofmyocardial CTGF were obviously decreased, the protein expression of myocardialCu-Zn-SOD and plasma adiponectin levels were obviously increased in type 2diabetic rats.Telmisartan could down-regulate the over-expression of myocardial Nox4 andp22phox mRNA and CTGF protein, up-regulate the expression of myocardialCu-Zn-SOD protein, lessen the myocardial oxidative damage and produce theprotective roles on the myocardium in diabetic rats. |
PDF Full Text Request