芩丹膠囊論文：芩丹膠囊高血壓自發(fā)性高血壓大鼠外膜重構Ⅰ、Ⅲ膠原

1、構I、皿膠原【中文摘要】1.觀察苓丹膠囊對自發(fā)性高血壓大鼠血壓的影響。2.觀察苓丹膠囊對血管外膜I、皿膠原表達的影響，并探討苓丹膠囊逆轉高血壓血管外膜重構的機制。方法1.研究對象：32只40周齡雄性SHF大鼠隨機分為4組,模型組（SHR組）、苓丹膠囊大劑量組（SHR+QD組）、苓丹膠囊小劑量組（SHR+QD組）、氯沙坦組（SHR+Los組）,另設40周齡雄性WKY大鼠16只分為空白對照組（WKY空白組）及正常藥物對照組（WKY+Q組）。SHR+Q給予苓丹膠囊750mg/(kgd);SHR+QD組給予苓丹膠囊150mg/(kgd);SHR+Los組給予氯沙坦30mg/(kgd);WKY+750m

2、g/(kg-d);WKY白組和SHF組給予相等劑量生理鹽水,1次/d,連續(xù)給藥12周各組大鼠在末次給藥后禁食24h,不禁水。10%水合氯醛腹腔注射麻醉后進行后續(xù)實驗。2.研究內容：（1）大鼠尾動脈收縮壓測定。（2）免疫組化法觀察胸主動脈外膜I皿膠原表達。（3）實時定量PCR僉測胸主動脈外膜I、皿膠原表達。用westernblotting檢測I膠原蛋白表達。結果1.各組大鼠治療前后收縮壓比較見圖1,從給藥第4周起,SHR+QD組、SHR+QD組、SHR+Lo組分別與SHR1比較,血壓下降明顯，其差異均具有統(tǒng)計學意義（P0.05）,SHR+QDH組與SHR+QDL組比較差異有統(tǒng)計學意義（P0.05

3、）。3.主動脈壁I、皿膠原mRNA表達水平比較采用2-Ct方法，將I、皿型膠原基因表達Ct值轉換為相對于WKY空白組的變化倍數(shù)，可以直接得到的基因相對于參照基因的定量。如圖6和7所示分別為I、皿膠原的擴增、溶解曲線和溶解峰，說明I、皿膠原是特異性基因表達，無引物二聚體及非特異性擴增。研究結果顯示：見圖4,WKY空白組和WKY+1間差異無統(tǒng)計學意義(P0.05),SHR+QDH組和SHR+QD組間差異有統(tǒng)計學意義(P0.05),SHR+QDH組和SHR+QDfi間差異有統(tǒng)計學意義(P0.05)。結論芩丹膠囊對SHR大鼠有顯著的降壓療效，其降壓機制與芩丹膠囊降低SHR大鼠I、皿膠原表達水平有關，同

4、時與逆轉血管外膜重構，抑制外膜纖維化，減少I、皿膠原在外膜的合成與沉積有關?！居⑽恼緼iml.ObserveQindancapsuleonbloodpressureinspontaneouslyhypertensiverats.2.ObservetheQindancapsuleonvascularadventitiaI,皿collagenexpression,andtoexplorethereversalofhypertensivevascularadventitiaremodelingmechanism.Methods1.Study:32SHRratsof40weeksoldwerera

5、ndomlydividedinto4groups,themodelgroup(SHRgroup),Qindanhighdosagegroup(SHR+QDHgroup),Qindanlowdosagegroup(SHR+QDLgroup),theLosartangroup(SHR+Losgroup),Besides,16WistarKyoto(WKY)ratsofthesameweeksweretakenasthenormalcontrol(WKYfcontrolgroup)andQindangroup(WKY+QDgroup).SHR+QDHgroupwastreatedwithhighdo

6、sage750mg/(kgd);SHR+QDgroupwastreatedwithlowdosage150mg/(kgd);SHR+Losgroupwasgivenlosartan30mg/(kgd);WKY+QDgroupweretreatedwithhighdosage750mg/(kgd);WKYandSHRcontrolgroupweregivenanequaldosageofsaline,onceaday,continuousadministrationfor12weeks.Ratsineachgroupafterthelastadministrationinthefasted24h

7、,cannothelpbutwater.Alltheratswereanesthetizedwithintraperitonealinjectionof10%chloralhydratefollow-upexperiments.2.Research:。)Determinationofrattailarterysystolicpressures.(2)ObservedaorticadventitiaI,皿collagenbyimmunohistochemistry.(3)Real-timequantitativePCRdetectionofthoracicaorticadventitiaI,皿c

8、ollagen.(4)WesternblottingdetectionofexpressionofIcollagen.Results1.ComparisonofsystolicbloodpressureofratsFig1,after4weeksfromtheadministration,Qindanhighdosage,lowdosagegroup,andlosartangroupcomparedwiththemodelgroupbloodpressuredecreased,thediffereneewasstatisticallysignificant(P0.05),Qindanhighdosagegroupcomparedwiththelowdosagegroupwasstatisticallysignificant(P0.05).3.AorticwallI,皿collagenmRNAexpressioncomparedUsing2-Ctmethod,typeI,皿collagengeneexpressionrelat