The Protective Effect Of Anti-inflammation On Organ Damage In Sinoaortic Denervated Rat

Blood pressure(BP) is not stable during the 24h period. This spontaneousvariation of BP is defineded as "blood pressure variability (BPV)". Rat ofchronic sinoaortic denervation(SAD) is characterized by its high BPV and a normalBP level. Our previous stUdies have found that BPV is a contributing factor of endorgan damage (EOD), Which includes myocardial hypertrophy, vascularremodeling, kidney damage and so on. But the mechanism why organs damageproduced is still unclearInflammation is a defensive reaction of the body to injtIry factors and a paradoxprocess of injury and anti-injury. Recent researches have demonstrated thatmechanica1 stimulation or stretch can induce inflammation. Our previous study alsoshows that infiarnmatory factors were concemed with organs damage in SAD rats.Therefore, we put forward a hyPothesis tha organs damage in SAD ratS is concemedwith inflammation.Method:Following contents are included in this stUdy:l. SAD model: SAD was pefformed in male Sprague-DaWey rats at the age ofl0 weeks. ContrOl tals were sham-opefated.2. Determination of factors related to inflammation and pathological evalUationof oMs damage: l6 weeks after sinoaortic denervation or sham operation,the serumal, or plasmal, or tissue level of indexes related to inflarnmationwere observed. These indexes included TXB2, IL--l, TNF-- Q and reactiveoxygen species (ROS): and pathological evaluaion of organs damageincluded hydroxyProline (in myocardial and in blood vessels). collagenvolume fraction in myocardial, collagen volume fraction in blood vessels,glomerulus damage score and number of infiltraing inflanunatory cells.StatiStical analysis was pefformed with sham-opefated fats as colltrol.3 - Determination of factors related to inflanunation and pathological evaluationof organs damage after ani-indarnmatory theraPy 5 weeks after SAD, ratsreceived a 12-week period of indomethacin (20mg/kg/d, po), or atenolo1(20mg/kg/d, po), or vitaInin E (l00mg/kg/d, po) resPectively. Famotidine andtripotaSsium dicitrae bismuthate were administraed with indomethacin forprotCction of gastric mucosa. Drugs were adIninistraed accUraely bysingle-caged. Indexes mentioned above were determined after execlltion ofthe SAD rats. Statistical analysis was perfOrmed with SAD rats as controlgrouP.Results:l .Levels of factors related to inflarnmation betWeen Yats of l6 weeks after SADand l6 weeks after sham-operation: TXB2(SAD vs Sham: 302I l39ng/L vsl23 f3lng/L), TNF Q (SAD vs Sham: 34.8 l6.5ng/L vs 6.40 f l .23ng/L),IL--l(SAD vs Sham: 92.9i40.2ng/L vs 3.8f2.2ng/L) and ROS(SAD vsSham: myocardial tissue: l80 l 55UhagPro vs 55.8 l l l .7UhagPro, lddney:l075 f l72U/mgPro vs 247 l 40U/IngPro) increased markedlyto<0.0l);pathological observation fotmd that the axnoun of inLfiltrating inflammatorycells increased obviously, the degree of myocardial and blood vessel fibrosisaggrevated(SAD vs Sham: myocardial hydroxyProline: 75.9l25.2wi vs44.2t20.0ndg, blood vessels hydrOxyProline: l598t375~g vs l064i329ngg); collagen volume fraction in left ventrcle(SAD vs Sham: l4.l f3.9% vs 4.l t l.7%), collagen volum fraction in blood vessel (SAD vsSham: 43.3 f 5.2% vs 32.0 i 3.6%) and glomerulus injury score of the kidney(SAD vs Sham: 52.2 i l0.4% vs 24.0 l 7.9 )also significanly increased.2.Levels of indexes related to inflammation after a l2 weeks ani-inflanunationthWY' TXBz(Indo, Aten, MtE vs control: l68l66, l36i44, l45l33 vs302f l39ng/L), IL-l (Indo, Aten, WtE vs SAD: 36.4f22.l, 4l.6l l0.5, 36.8fl3.l vs 92.9i40.2ng/L) and ROS (myocardal tissue: hido, Aten, VitE vscontrol: l30 l 29, l05 t 30, l27 t 37 vs l80 f 55Mro; kidney: Indo, Aten,Vith vs control: 470t l25, 648 t l9l, 64l f263 vs l075 t l72U/IngPro)significanily decreased. M Q (Indo, Aten, Vnd vs SAD: 35.4 t 7.9, 37.8 f3.8, 62.7f59.2 vs 34.8 f6.5ng/L) had not a significan change. Pathologicalobservation found that after ani-inflammation theraPy, the am...