The Influence On Regeneration And Repair In Acute Renal Tubular Injury By The Inhibitory Proliferation Effect Of Angiotensin Blockades

Background and objective: Since angiotensin converting enzyme inhibitors(ACEIs) and angiotensin receptor blockades (ARBs) as representative of angiotensinblockades (ABs) have been applied to clinical treatment, most researches are concernwith beneficial protection. However, with ABs are more widely and long-term clinicalapplications, some clinical trails and evidence-based medicine data find thatangiotensin blockers in the treatment of the kidney disease may be complicated byacute kidney injury(AKI). Most studies suggest that kidney bloodperfusion reductionwas causes by the antihypertensive effect is mainly reason,while whether the effectsof surpressing proliferation of ABs in occurrence of kidney injury have lessattention.Constructing gentamicin-induced acute tubular injury rattus models,angiotensin blockers intervene in rattus models,beta blockers as a control,mensuratingserous creatinine and urea to observe the change of renal function, estimating theeffects of ABs to hemodynamics by measuring BP, observing proliferative status ofrenal tissues and cells by immunochemical staining method, mensurating theconcentration of plasmic angiotensin Ⅱ(AngⅡ) and the expression of angiotensinⅡtype1receptor(AT1R) and angiotensinⅡ type2receptor (AT2R) of renal tissues inorder to investigate the mechanism of angiotensin blocker-induced acute kidneyinjury, and to provide a theoretical basis for clinical safety applicationsMethods: Adult Sprague Dawley rats receive intraperitoneal injection ofgentamicin to build acute renal tubular injury model. All rats are randomly dividedinto normal groop, gentamicin group, metoprolol group, valsartan group, fosinoprilgroup and fosinopril-valsartan group according to different levels of intervention. Ratstail blood pressure is measured at three time point (1st week,2nd week,3rd week), each group’s blood are collected. And other renal samples are collected at themeantime after rats are executed.Then mensurating value of serous creatinine; ureaand plasmic AngII.HE pathological staining observe changes in renal,immunochemical staining mensure expression of PCNA. Expression of AT1R mRNAand AT2R mRNA are mensurated by real-time PCR assay. All data are analyzed bySPSS11.5.Result:(1) Tail BP of gentamicin group is higher than normal and other group,other time point have not significantly difference;(2) The levels of creatinine of thosemodel groups at1nd and2nd week are increase (P<0.05), but it recover nomal at4ndweek.(3) The BUN of each model group was significantly higher than the normalgroup (P<0.05), valsartan group, fosinopril and fosinopril+valsartan group increasedthan the normal and metoprolol group (P <0.05);(4)The levels of plasmic angiotensinⅡ, saline group, metoprolol group and valsartan group are significantly higher thanother groups (P<0.05) at1st and2nd week,it recover nomal at4nd week;Thefosinopri and fosinopril-valsartan group have on significantly than normal group.,butfosinopril-valsartan group decreae at4nd week(P<0.05);(5). The results of HEstaining indicate that renal injury of fosinopril groop, valsartan groop andfosinopril-valsartan groop is severely than other model groops, and pathologic statecontinue to4th week, while renal morphology of saline groop and metoprolol groupdid not change.(6) The expression of PCNA of valsartan groop, fosinopril group andfosinopril-valsartan group is significantly lower than saline group and metoprololgroup (P<0.05) at1st and2nd week, while higher at4th week (P<0.05).(7).Theexpression of AT1R and AT2R mRNA of all model groups is higher than normalgroup (P<0.05) at1st week. The AT1R mRNA expression of Gentamicin group, themetoprolol group and fosinopril group was increased (P <0.05) and other groups isnormal at2nd weeks; each model group AT2R mRNA expression was elevated(P<0.05); AT1R mRNA expression is normal at4nd weeks, AT2R mRNA expressionhas significantly higher with angiotensin intervention compared to the normal group,gentamicin group alone, the metoprolol group was.and valsartan group (P<0.05).Conclusions:(1) ABs delays the recovery of renal function and structure in gentamicin-induced renal injury rats. Dual-blockade with ACEI and ARB isn’t moreefficacious than solo application of ACEI/ARB.(2).the effect of angiotensin blockerson hemodynamics is not major factors in its inducing acute kidney injury.(3). theinhibitory proliferation effect of Angiotensin Blockades involves in the occurrence ofinduced acute kidney injury, ACEI involve in the occurrence of induced acute kidneyinjury by reducing angiotensinⅡto inhibit proliferation, ARB involve in theoccurrence of induced acute kidney injury by reducing expression of AT1R to inhibitproliferation.