Study On The Mechanism Of Mongolian Medicine Leonurus Alba Intervening In Vascular Remodeling In Spontaneously Hypertensive Rat

Objective:Vascular remodeling is the most basic pathological change of cardiovascular and cerebrovascular aging or related diseases.The study investigates the intervention mechanism of Mongolian herbal Baiyimucao(Panzerina lanata)on vascular remodeling in SHR.It is of great significance to guide clinical prevention and treatment of cardiovascular diseases.Methods:Five-week-old WKY and SHR rats were used as experimental subjects,WKY rats were used as control group,and SHR rats were divided into five groups,including control group(SHR-C),low-dose group of Baiyimucao(BYMC-L,0.22 g crude drug/kg),high-dose group of Baiyimucao(BYMC-H,1.12 g crude drug/kg),Losartan group(20 mg/kg/d)and Atorvastatin group(10 mg/kg/d).From 6th week,SBP,DBP and PP of rats were dynamically monitored once every two weeks by noninvasive tail artery method until 22 weeks;Using H&E staining to observe the pathology of vessel and using picrosirius red staining to observe collagen and elastic fibers in thoracic aorta and carotid artery;observing fibrosis in heart and kidney tissues by Masson staining;polarized light microscopy was used to observe the sub-types of collagen fiber,and inverted fluorescence microscopy was used to observe elastic fiber morphology and distribution;the expression of α-actin and AT1 in vessels was detected by IHC staining;Elisa and chemical reaction methods were used to detect the level of vasoactive substances,including Renin,Ang II,ALD and ET-1,blood lipid components,including TC,TG,HDL-C and LDL-C,and liver and kidney function parameters,including Cr,BUN,GOT and GPT.Results:(1)The intervention effect of drugs on vascular remodeling in SHR and the potential mechanism.Hyperplasia and structural changes of thoracic aorta and carotid artery in SHR control group were significant,with obvious increase in WT,ID,WLR and the number of VSMC(P<0.05)and abundant diploid cells;collagen depositions were increased in the wall(P=0.005);the expression ofα-actin reduced 23%(P=0.036),while AT1 increased 7%in the thoracic aortic wall;and the expression of α-actin and AT1 reduced by 38%and 13%in the carotid artery wall.Compared with the SHR control group,Baiyimucao significantly decreased WT(6%/14%),ID(2%/13%),WLR(9%/19%),the number of VSMC(18%/19%),Collagen deposition(20%/16%)and the expression of AT1(22%/12%),increased the expression of α-actin(11%/44%);Atorvastatin decreased WT(7%/12%),ID(3%/3%),WLR(6%/18%),the number of VSMCs(19%/28%),Collagen deposition(18%/9%)and the expression of AT1(34%/0%),increased the expression of α-actin(14%/31%).And all drugs ameliorated collagen deposition and vascular remodeling in SHR.(2)The effects of Baiyimucao on the RAAS system and vascular terminal organs in SHR.Compared with WKY control group,the Renin,Ang Ⅱ,ALD and ET-1 levels of the SHR control group increased(P<0.05);compared with the SHR control group,Baiyimucao significantly decreased Renin(12%),Ang Ⅱ(4%),ALD(12%)and ET-1(31%)levels,the myocardial cell volume became smaller,the left ventricular hypertrophy was improved,and the collagen fibers in the heart tissue were reduced by about 3%,the glomerular volume and glomerular space were significantly ameliorated,and the collagen fiber expression in the kidney reduced by about 3%.Only Renin levels decreased more in Atorvastatin treated groups than in Baiyimucao,while Ang Ⅱ increased by 8%(P=0.023).The level of TC,TG,HDL-C and LDL-C in the plasma of SHR control group were lower than those in the WKY group.Until to 23 week,there were no statistically significant differences in plasma BUN,Cr,GOT,and GPT between groups.(3)The effect of drugs on blood pressure.Compared with WKY control group,SBP,DBP,and PP were significantly increased in the SHR untreated group(P<0.05).Compared with the SHR control group,the overall SBP value of Baiyimucao and Atorvastatin groups was lower than about 5 mmHg;DBP value of drug-treated group was higher than control group from 16 to 22 weeks by 5-10 mmHg;PP levels of low-dose group at weeks 8,10,and 14(P=0.034,0.046 and 0.007),and of high-dose group at weeks 8 and 10(P=0.000 and 0.002)were significantly lower;the PP value of drug-treated group was about 5-10 mmHg lower than that of the control group;Losartan administration could effectively reduce SBP,DBP,and PP values in SHR(P<0.05).Conclusion:(1)Baiyimucao decreased WT,WLR,and the number of VSMC and collagen deposition in the wall of thoracic aorta and carotid artery,increased the expression of α-actin and decreased the expression of AT1,thereby improving vascular remodeling in large and medium arteries and exerting vascular protective effect,which improves carotid vascular remodeling better than thoracic aorta.(2)Baiyimucao decreased the vasoactive substances Renin,AngⅡ,ALD and ET-1 associated with RAAS and improved the degree of fibrosis and tissue structural abnormalities in the heart and kidney of vascular terminal organs.There was no obvious abnormality of liver and kidney function after 16 weeks of administration.(3)Baiyimucao had a slight lowering effect on SBP,also reduced PP.In conclusion,Baiyimucao reduced ECM components,including the deposition of collagen and the degradation and disturbance of elastic fibers in the wall,by reducing the level of vasoactive agents,inhibiting RAAS activation,and avoiding the stimulation of VSMCs.Eventually it ameliorated vascular remodeling and the damage of the heart and kidney of end organs,while preventing the occurrence of hypertensive complications.