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Effect Of Pancreatic Kininogenase On Left Ventricular Hypertrophy In Spontaneously Hypertensive Rats And Possible Mechanism

Posted on:2007-08-08Degree:MasterType:Thesis
Country:ChinaCandidate:P DuFull Text:PDF
GTID:2144360182996463Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
LVH is one of the severe complications of hypertension. It isapproved that LVH is an independent risk factor which aggravatescoronary heart disease, heart failure, stroke and so on. So reversingLVH becomes the ultimate goal of therapy to hypertension. Nowresearchers pay much attention to ACEI and ARB which can reverseLVH. Others, such as β-blocker, calcium antagonist, diuretics, are alsoapproved to have a function of reversing. But above-mentionedvarious medicines all have certain taboo diseases and side-effects, so itis necessary to research a new medicine to prevent and cure LVH.Pancreatic kininogenase is a kind of bio-chemical medicine which isforbidden to used for the patients who have already bled tendency. Ithas no obvious side-effects. Now it is applied in the field of diabetesand curative effect is good .We choose spontaneously hypertensiverats as research object and investigate the effect of pancreatickininogenase on LVH and possible mechanism. In this experiment, 24 fifteen-week male SHRs were randomlydivided into three groups: SHR control group, low-dose and high-dosegroup, 8 rats each group. Same age male WKY rats who have normalblood pressure were served as control group (n=8). Low-dose group(7.2U·kg-1·d-1) and high-dose group(14.4U·kg-1·d-1) were treatedwith pancreatic kininogenase through abdominal injection. SHRcontrol group and WKY group were given with 0.9% saline. Every ratwas injected once a day and it was lasted for 4 weeks. Systolic bloodpressure were measured by BL-420 biology enginery experimentsystem after drug therapy. The concentration of serum NO, SOD,MDA were measured. Opened thorax and took out the heart quickly,then weighed the left ventricular (LVW) and made out the ratio ofLVW and BW. Myocardial tissue was stained with VanGieson, thenCVF and PVCA were measured for the purpose of investigating theeffect of myocardial fibrosis. The structure of myocardial vessel wasobserved by HE. Myocardial ultrastructure of each group wasobserved under the electron microscope. SPSS 11.5 was used toanalyze all data.This experiment showed that SHR at 20 week-ages exhibitedhigher SBP,LVMI,CVF,PVCA compared with WKY rats. It meantthat LVH had come into being. SBP,CVF,PVCA of treated groupswere obviously decreased after drug therapy of pancreatickininogenase for 4 weeks, but there was difference with WKY rats(P<0.05). SHR had lower NO,SOD, but higher MDA compared withWKY group (P<0.05). The concentration of NO,SOD had increasedsignificantly in treated groups ,while MDA had decreased. And therewas no remarkable difference with WKY rats. It was discovered byHE that pancreatic kininogenase can reverse the incrassated vesselwall, decrease the ratio of vessel wall and cavity. Collagen distributedmostly around myocardial coronary artery. Collagen was most in SHRcontrol group, while a little collagen fibril in WKY group. In bothtreatment groups, collagen decreased around coronary artery. Itshowed pancreatic kininogenase can reduce myocardial fibrosis.Under electron microscope, the quantity of mitochondrion increased inSHR control group. At the same time, the mitochondrion was swellingand muscular fibres fractured. The change of myocardial ultrastructurewas small in both treatment groups. Pancreatic kininogenase canrecover the myocardial ultrastructure.We can draw such conclusions from this experiment: Pancreatickininogenase can reverse LVH of SHR rats, inhibit the collagensynthesis and inhibit the remodeling of myocardial vessel. We guess itconcludes such mechanism:① It can reduce SBP of SHR. ② It canreverse LVH by increasing SOD and decreasing MDA. ③ It canincrease the concentration of serum NO, so it reverses LVH.
Keywords/Search Tags:pancreatic kininogenase, spontaneously hyperten-sive rats, left ventricular hypertrophy, oxidative stress, nitric oxide, myocardial ultrastructure
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