Protective Effects And Mechanisms Of Oral Administration Of Tongxinluo On The Aorta Of STZ Induced Diabetic Rats

Objective To study the protective effects and mechanisms of Tongxinluo capsule on the function and structure of the aorta of the STZ induced diabetic rats.Method 15 rats were chosen randomly from 60 healthy male Wistar rats as normal control rats(C group,n=15)after 12 hours of fasting,and 1%freshly prepared STZ solution was injected intravenously(55 mg/kg body weight)through tail vein into the rest 45 rats to induce diabetes.Only rats with blood glucose higher than 16.7 mmol/L after three days were considered as being diabetic in the fasting state.And 40 successfully established diabetic rats were randomly divided into untreated diabetic rats(DM group,n=20)and Tongxinluo-treated rats(TXL group,n=20).Prior to sacrifice after 24 weeks of diabetes,animals were weighted.Then after animals were fasted overnight(18 h),under 10%chloral hydrate(350 mg/kg,ip)anesthesia,two polyethylene cannulas were inserted into the aorta via the left carotid and left femoral arteries for central and peripheral blood pressure measurements,respectively.And PWV,elastic modulus and wall stress were calculated.At the end of the hemodynamic measurements,blood was collected for biochemical,HbAlc and AGEs determination. Then after rats been sacrificed,a 1-cm sample of the descending thoracic aorta was excised,and sections were stained with HE and PAS for the determination of aortic pathological changes and other indexes.Moreover,immunohistochemistry was used to determine the RAGE and CTGF expression in aortas.Results(1)Compared with untreated diabetic rats,Tongxinluo-treated diabetic rats has no significant amelioration in blood glucose and AGEs level(P＞0.05),but body weight increased(P＜0.01).(2)The PWV and elastic modulus of untreated diabetic rats significantly increased(P＜0.05)compared with those of control rats,while the PWV and elastic modulus of Tongxinluo-treated diabetic rats are bigger than those of untreated diabetic rats(P＜0.05).There is no apparent difference among the rats of the three groups in wall stress.(3)All the diabetic rats' aortas had obvious injury when observed under light microscope,but those in Tongxinluo-treated rats were much better.(4)The expression of RAGE and CTGF in untreated diabetic rats was much higher than that of control rats,and Tongxinluo could decrease the expression.Conclusion RAGE plays an important role in mechanisms of aortic injury in diabetic rats,and Tongxinluo may alleviate the injury through the down regulation of RAGE.