| Objective: To investigate the antihypertensive effect and the effect on the vascular protection and its possible mechanism of Dilongjiangya capsules by detect the changes of tail arterial blood pressure,serum biological active substances and pathological changes of the thoracic aorta and related gene and proteins in spontaneously hypertensive rats.Methods: 8 weeks old male WKY rats 8 for normal controls as WKY group,and male SHR rats 40 were fed for 1 week,measuring blood pressure,numbered and randomly divided into 5 groups according to the systolic blood pressure values: model group,high dose group of Dilongjiangya capsules,middle dose group of Dilongjiangya capsules,low dose group of Dilongjiangya capsules,benazepril group,8 rats per group.Dilongjiangya capsules intervention group,gave Dilongjiangya capsules suspension liquid by lavage with low dose of 126 mg/kg,middle dose group of 252 mg/kg,high dose group of 504 mg/kg,respectively.The captopril group gave benazepril hydrochloride suspension liquid 0.9 mg/kg by lavage.Model and WKY group were given equal volume of distilled water.All rats were given once daily for 9 weeks.The changes of single administration and continuous administration of rats' systolic and diastolic blood pressure in rat tail artery and weight were measured.After the end of the experiment,rats were anesthetized by intraperitoneal injection.Taken blood from the heart,vertebral death,separation of the thoracic aorta.The content of NO in serum was measured by nitrate reductase method.The levels of serum ET-1,CA,Renin,Ang? and Ald were measured by ELISA.The pathological changes of thoracic aorta was observed by HE and Masson staining.The expression of AT1 R mRNA in thoracic aorta was detected by RT-PCR.The expression of TGF-?1 and VEGF in thoracic aorta was measured by blotting.Rseults:(1)In the course of the experiment,the rats in the WKY group were always normal,the activity was flexible,they were not easy to stir up,and no obvious resistance,aggressive behavior and body weight increased with the increase of age.The rats in the model group were always irritable,strong resistance and aggressive behavior.The rats in Dilongjiangya capsules each dose group were gradually recovered after 2 weeks of continuous administration,which was more stable than the model group,activities,ease of crawling,aggressive behavior significantly reduced.There was no significant difference in body weight between the experimental groups(P>0.05).(2)With single-dose drug delivery: Compared with the WKY group,the systolic blood pressure of the model group was significantly higher than that of the model group(P<0.05).Compared with the model group,the systolic pressure began to decrease after 1 hour in the high dose group and the benazepril group,and the difference was statistically significant after 2 hours(P<0.05).The systolic blood pressure began to decrease in the low dose group and middle dose group after 2 hours and the difference was statistically significant at 4 hours(P<0.05).Compared with WKY rats,the diastolic blood pressure of the model group was significantly higher than that of the model group(P<0.05).Compared with the model group,the diastolic blood pressure of the rats in the high dose group and the benazepril group began to decrease after 1 hour and the difference was statistically significant after 2 hours(P<0.05).The diastolic blood pressure began to decrease in the low dose group and middle dose group after 2 hours and the difference was statistically significant at 4 hours(P<0.05).With continuously drug delivery: Compared with the WKY group,the systolic blood pressure of the model group was significantly higher(P<0.05).Compared with the model group,the systolic blood pressure began to decrease steadily at the first week of continuous administration in the benazepril group(P<0.05),at the second weeks in the high dose group(P<0.05),at the third week in the middle dose group(P<0.05),and the 5th in the low dose group(P<0.05).Compared with the WKY group,the diastolic blood pressure of the model group was significantly higher(P<0.05).Compared with the model group,the diastolic blood pressure began to decrease at the first week of continuous administration in the benazepril group(P<0.05),at the third weeks in the high dose group(P<0.05),at the 5th week in the middle dose group(P<0.05),and the 9th in the low dose group(P<0.05).(3)Compared with the WKY group,the serum CA was elevated in the model group(P<0.05).Compared with the model group,the serum CA in the Dilongjiangya capsules high and middle dose groups decreased(P<0.05)and there was no significant decrease in the Dilongjiangya capsules low dose group(P>0.05)(4)Compared with the WKY group,the levels of serum Renin,Ang?and Ald in the model group were significantly higher than those in the control group(P<0.05).Compared with the model group,the levels of Renin in the Dilongjiangya capsules high and middle dose groups decreased(P<0.05),Ang? and Ald in Dilongjiangya capsules each dose group were significantly lower(P<0.05),and the levels of Renin and Ald in the high dose group were significantly lower than those in the low dose group(P<0.05).(5)Compared with WKY group,serum NO decreased and ET-1 increased in model group(P<0.05);Compared with model group,Dilongjiangya capsules each dose group of serum NO elevated,ET-1 lower(P<0.05),the serum NO obvious higher in the Dilongjiangya capsules high and middle dose group NO than low dose,the difference was statistically significant(P<0.05).(6)WKY group had complete intima,and the muscle fibers were evenly arranged around the vascular lumen.There was no obvious smooth muscle cell proliferation.The outer membrane and the middle membrane were clear and the thickness was moderate.In the model group,obviously,incomplete,significantly thickening of the membrane,muscle fibers arranged very irregular,different thickness,smooth muscle cell proliferation was obvious,the outer membrane and the membrane boundaries were unclear and significantly thickened;In Dilongjiangya capsules each dose group and benazepril group,the pathological changes of the group were improved in different degrees.The intima of the rats in each group was more smooth and the middle layer of muscle fibers were arranged neatly.In the high,middle dose groups and benazepril group,the thickness of membrane were reduced.Rats thoracic aorta muscle fibers were dyed red,collagen fibers were stained blue and the nuclei were dark brown.Compared with the WKY group,the content of collagen fibers in the thoracic aorta of the model group was significantly increased(P<0.05).Compared with the model group,the content of collagen fibers in the thoracic aorta of Dilongjiangya capsules each dose group were decreased(P<0.05).(7)Compared with the WKY group,the expression of AT1 R mRNA in the model group were significantly up-regulated(P<0.05).Compared with the model group,the expression of AT1 R mRNA was down-regulated in the Dilongjiangya capsules each dose group(P<0.05).The expression of AT1 R mRNA in the Dilongjiangya capsules high dose group was significantly lower than that of the low dose group(P<0.05).(8)Western blot analysis showed that the expression of TGF-?1 and VEGF protein in model group was significantly higher than that in WKY group(P<0.05),the difference was statistically significant.Compared with the model group,the expression of TGF-?1 in the Dilongjiangya capsules high and middle dose groups decreased and the expression of VEGF protein in the Dilongjiangya capsules each dose group decreased the difference was statistically significant(P<0.05).Conclusions:(1)Dilongjiangya capsules can effectively reduce the systolic and diastolic blood pressure of SHR,and the antihypertensive effect is slow and lasting,and it is time and dose dependent.(2)The antihypertensive effect of Dilongjiangya capsules may be achieved by inhibiting the catecholamine levels and the excessive activation of RAAS system and improving hypertensive vascular injury.(3)The possible mechanism of Dilongjiangya capsules to improve the vascular injury of SHR is to regulate the coordination state of ET-1/NO and reduce the circulating level of Ang? so that the level of AT1 R gene is down-regulated,TGF-?1 and VEGF protein expression were reduced. |
PDF Full Text Request