CAJ | 학술논문

目的对比重组人生长激素(rhGH)与骨髓间质干细胞(MSCs)单用或联用对阿霉素性心肌病心力衰竭(心衰)大鼠的疗效.方法将Wistar大鼠分为正常组6只、心衰组9只、rhGH组6只、MSCs组7只和rhGH与MSCs联合治疗(G+M)组7只.MSCs移植经心肌内点状注射,rhGH2 mg/kg,隔日1次,皮下注射.1个月后行左室功能、全心质量指数(HW/BW)及左室质量指数(LW/BW)测定.免疫组化观察MSCs在心肌内的分布,聚丙烯酰胺凝胶电泳分离心肌肌球蛋白重链(MHC)同工酶V1和V3型.治疗前后测定血清生长激素(GH)和B型利钠肽(BNP)浓度.结果与心衰组比较,MSCs组心功能各指标均无有统计学意义的改变,rhGH组左室收缩压和左室内压力最大上升速率升高,G+M组左室收缩压和左室内压力最大上升及下降速率均升高,均为P<0.05.三个治疗组HW/BW和LW/BW均较心衰组有降低,但P>0.05.G+M组心肌内MSCs数量多于MSCs组.与心衰组比较,rhGH组V1型MHC(V1)、v3型MHC(V3)、V1/V3比值差异无统计学意义,MSCs组V3增加,G+M组V1和V3增加,均为P<0.05;与rhGH组比较,MSCs组V3增加,G+M组V1和V3均增加,均为P<0.05;与MSCs组比较,G+M组V1增加,P<0.05.GH水平在治疗前均较正常组降低,P<0.05;治疗后均较心衰组增高,P<0.05,但仅接近正常水平,各组间比较差异无统计学意义.BNP水平在治疗前均较正常组升高,P<0.05;治疗前后比较,rhGH组和G+M组差异有统计学意义,P<0.05和P=0.001.结论 rhGH治疗可改善阿霉素性心肌病心衰大鼠的心脏收缩功能,MSCs移植未见明显疗效;二者联合治疗可提高MSCs存活率,增加MHC含量,改善心脏收缩和舒张功能.
목적 대비중조인생장격소(rhGH)여골수간질간세포(MSCs)단용혹련용대아매소성심기병심력쇠갈(심쇠)대서적료효.방법 장Wistar대서분위정상조6지、심쇠조9지、rhGH조6지、MSCs조7지화rhGH여MSCs연합치료(G+M)조7지.MSCs이식경심기내점상주사,rhGH2 mg/kg,격일1차,피하주사.1개월후행좌실공능、전심질량지수(HW/BW)급좌실질량지수(LW/BW)측정.면역조화관찰MSCs재심기내적분포,취병희선알응효전영분리심기기구단백중련(MHC)동공매V1화V3형.치료전후측정혈청생장격소(GH)화B형리납태(BNP)농도.결과 여심쇠조비교,MSCs조심공능각지표균무유통계학의의적개변,rhGH조좌실수축압화좌실내압력최대상승속솔승고,G+M조좌실수축압화좌실내압력최대상승급하강속솔균승고,균위P<0.05.삼개치료조HW/BW화LW/BW균교심쇠조유강저,단P>0.05.G+M조심기내MSCs수량다우MSCs조.여심쇠조비교,rhGH조V1형MHC(V1)、v3형MHC(V3)、V1/V3비치차이무통계학의의,MSCs조V3증가,G+M조V1화V3증가,균위P<0.05;여rhGH조비교,MSCs조V3증가,G+M조V1화V3균증가,균위P<0.05;여MSCs조비교,G+M조V1증가,P<0.05.GH수평재치료전균교정상조강저,P<0.05;치료후균교심쇠조증고,P<0.05,단부접근정상수평,각조간비교차이무통계학의의.BNP수평재치료전균교정상조승고,P<0.05;치료전후비교,rhGH조화G+M조차이유통계학의의,P<0.05화P=0.001.결론 rhGH치료가개선아매소성심기병심쇠대서적심장수축공능,MSCs이식미견명현료효;이자연합치료가제고MSCs존활솔,증가MHC함량,개선심장수축화서장공능.
Objective To investigate the therapeutic effects of recombinant human growth hormone (rhGH)and mesenchvmal stem cells(MSCs) transplantation alone or in combination in adriamycin.indnced cardiomyopathv(CM)mt model.Methods Wistar rats were divided into normal(n=6).CM(n=9),rhGH(2 mg/kg,subcutaneous injection,qed for 1 month,n=6),MSCs transplantation(MSCs group,5×106/100,n=7)and rhGH+MSCs(G+M group,n=7)groups.After l month,hemodynamic data,the ratio of heart weight/body weight(HW/BW)and left ventricular weight/body weight(LW/BW)were obtained.The myocardial MSCs marked bv BrdU were detected by immunohistochemistry.Cardiac myosin heavy-chain(MHC)and its isozymes were detected by SDS-PAGE technique.Serum growth hormone(GH) and B-type natriuretic peptide(BNP)levels were measured.Results Compared to CM group.cardiac function remained unchanged in MSC group while significantly improved in rhGH group and further improved in G+M group.HW/BW and LW/BW were similar among groups(all P>0.05).The MSCs number in the myocardium of G+M group was significantly higher than those of MSCs group.Compared to CM group,V3·MHC was significantly inereased in MSCs group(10.33±0.33 vs7.43±2.08.P<0.05),V1 and V3.MHC were significantly increased in G+M group(86.22 4±1.73 VS 77.47±2.02.12.44±0.31 vs 7.43±2.08,all P<0.05).GH levels were significantly higher in rhGH and G+M treated animals than that in CM animals[(2.50±0.68) VS(1.37±0.09) g/L,(2.48±0.90) VS(1.25±o.42) g/L,all P<0.05],BNP levels were significantly lower in rhGH.MSCs and G+M treated groups than that in CM group [(1270.72±203.72) VS (1462.44±242.87) ng/L,(1385.00±250.13) VS (1475.29±281.33) ng/L, (1219.31±126.71) vs (1451.78±180.93) ng/L,all P<0.05].Conclusions rhGH but not MSC could improve the cardiac function in adriamycin.induced CM rats. Combined rhGH and MSCs transplantation therapy could further improve cardiac function possibly due to enhanced MSCs growth and transformation into cardiomyocytes.