Study on establishing hypertension animal models by adverse lifestyles and the antihypertensive effect of traditional Chinese medicine

OBJECTIVE Nowadays,with the living habits and diet structure changes,the morbidity and mortality of hypertension has been rising yearly,which induced by adverse lifestyles,excessive alcohol and poor diet.However,the animal models of hypertension resulted from adverse lifestyles have rarely been reported.It is essential to set up some more systematic models to study the characters of hypertension and evaluate the efficacy of traditional Chinese medicine(TCM).METHODS To build the rat model of human lifehabitual hypertension,SD rats had free access to alcohol with high-sucrose-fat diet(AHSFD),alcohol with high-fat diet(AHFD),high-sucrose-fat diet(HSFD),high-fat diet(HFD)and alcohol etc.Various of indicators were detected systematically to explore the features of hypertension models which included blood pressure(BP),liver and kidney functions,the lipid profiles and indexes quantifying TCM symptoms.Then we choose one of the stable and sustained animal models,studying the effects of RPA.E(which extracted from a TCM)on modulating the level of hypertension and the preliminary mechanism in this abstract.RESULTS ①The BP level,serum TC,TG,LDL-C of AHSFD-induced and AHFD-induced rats increased significantly,while the HDL-C reduced in the 4th week.② The BP level HSFD-induced rats increased significantly in the 6th week,serum TC,TG increased in 10 th week.③ The BP level of alcohol-induced rats increased significantly in the 9th week,serum TC,TG increased in 24 th week.④ The level of serum ALT,AST,UA and Cr of all model rats increased significantly after 12 weeks.Meanwhile the microcirculation increased significantly after8 weeks.⑤ After 4-week administration,RPA.E could significantly reduce BP of AHFD-induced hypertensive rats,and could reduce the serum TC,LDL-C,HDL-C,ALT,AST level after 8-week.CONCLUSION The rats induced by AHSFD,AHFD,HSFD and alcohol can raise BP obviously with underlying hepatic and kidney damage,the lipid profiles disorder and TCM symptoms change,while the AH(S)FD-induced hypertension models are earlier and more stable.RPA.E could mildly reduce BP level,and improve the lipid profiles disorders,hepatic damage,which reflects the characteristics of TCM on antihypertensive effects.The above models have their own characteristics,can be used to study the causes and pathogenesis of hypertension complicating metabolic disorder and the related treatment drug screening.

Combined antihypertensive effect of GSY and metoprolol,based on endothelium-dependent vasodilatation function

OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).

Exploration on the establishment of animal models for hyperuricemia and the application of traditional Chinese medicine

OBJECTIVE In recent years,the frequency of hyperuricemia has gradually risen along with the improvement of living standards,the irregular of diet and overfeeding greasy and surfeit flavor.However,hyperuricemia is a disorder of purine metabolism,and is strongly associated with insulin resistance and abnormal glucose metabolism.It is important to obtain a more stable and sustained animal model for the efficacy evaluation of traditional Chinese medicine(TCM).METHODS To manufacture the rodent model of hyperuricemia,the theory of increasing the source of the uric acid,reducing uric acid excretion and inhibiting uricase were used.We observed the influence on the serum uric acid and other indicators of rats induced by some factors:the lipid emulsion,high purine diet,beer with sugar,beer with sugar and high purine,and so on.Then we choose one of the stable and sustained animal models,studying the effects of Plo.E(which extracted from a TCM)on modulating the level of serum uric acid and the preliminary mechanism in this abstract.RESULTS ① At the 2nd week,the level of serum UA,BUN,Cr,TC,LDL-c of rats in the lipid emulsion group raised significantly.② At the 6th weeks,the serum UA in both the high purine diet group and lipid emulsion group raised obviously.③ The effects of Plo.E on hyperuricemia rats induced by high purine diet:After 8d administration,the Plo.E(three dosages)can reduce the UA level,and the middle and low dosages can reduce the TG level.After 25 dadministration,Plo.E can reduce the plasma viscosity,UA,TG,the whole blood viscosity level,the high dosage also can reduce the TC level.CONCLUSION The rats induced by the high purine diet and lipid emulsion can raised the serum UA obviously,while the way of lipid emulsion is earlier and more stable.Plo.E has a therapeutic effect on hyperuricemia,with an activity of reducing plasma viscosity and blood lipid.The above models conform to the pathogenesis of humans,can be used to study the causes and pathogenesis of hyperuricemia complicating metabolic disorder and the related treatment drug screening.

Combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet

OBJECTIVE Di.E and Gpm.E were separately extracted from two kinds of traditional Chinese medicine.The aim of this research is to investigate the combined anti-hyperuricemia effect of Di.E and Gpm.E on hyperuricemia rats induced by high-purine diet,and to study the underlying mechanism.METHODS Sprague Dawley(SD)rats were divided into some groups according to their serum uric acid(UA),the normal control group received standard diet,while others were fed with high-purine diet.After the success of modeling,SD rats were divided into 5groups according to UA:normal control group,model control group,Di.E and Gpm.E(high,middle,low dosages).The treatment groups were simultaneously orally administered.Two days before the last administration,the urine N-acetyl beta-D Glucosaminidase(NAG),Lysozyme(LYS)activity were separately detected using the urine collected from metabolic cage for 24 h.After the last administration,the blood was taken from postcava to detect the level:① The related indexes of liver and kidney function:the serum UA,blood urea nitrogen(BUN),creatinine(CR),alanine aminotransferase(ALT);② The uric acid metabolism related enzymes:the serum and liver xanthine oxidase(XOD),adenosine deaminase(ADA),guanine deaminase(GD),xanthine dehydrogenase(XDH)activity;③ Fibrosis related indexes of renal tissue:connective tissue growth factor(CTGF),monocyte chemotactic protein-1(MCP-1),TGF-β1,TNF-α,NF-κB levels.RESULTS Di.E and Gpm.E(high,middle dosages)could markedly reduce the serum UA level significantly,also can decrease XOD,ADA,TNF-α,MCP-1,NF-κB activity significantly.CONCLUSION The results show that Di.E and Gpm.E can decrease the serum UA level significantly,improve the liver and kidney function and slow down the process of renal fibrosis;the therapeutic effects may be related to their inhibition of XOD,ADA activity.