重组人生长激素和骨髓间质干细胞移植联合治疗阿霉素性心肌病心力衰竭的实验  

Therapeutic effects of recombinant human growth hormone and mesenchymal stem cells transplantation alone or in combination in adriamycin induced cardiomyopathy rat model

作　　者：李彦红[1] 王风芝[1] 

机构地区：[1]山西医科大学第二医院心内科,太原030001

出　　处：《中华心血管病杂志》2008年第9期794-798,共5页Chinese Journal of Cardiology

摘　　要：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，rhGH 2mg／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。Objective To investigate the therapeutic effects of recombinant human growth hormone （rhGH） and mesenchymal stem cells（MSCs） transplantation alone or in combination in adriamycin-induced cardiomyopathy （CM） rat model. Methods Wistar rats were divided into normal （ n = 6）, CM （ n = 9）, rhGH （2 mg/kg, subcutaneous injection, qod for 1 month, n = 6）, MSCs transplantation （ MSCs group, 5 × 10^6/100 μl, n = 7） and rhGH ＋ MSCs （ G ＋ M group, n = 7 ） groups. After 1 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 by 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 increased in MSCs group （ 10. 33 ±0. 33 vs 7.43 ±2.08 ,P 〈0. 05）, V1 and V3- MHC were significantly increased in G ＋ M group （86. 22± 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） μg/L, （2.48 ±0. 90） vs （ 1.25 ±0. 42） μg/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 n

关 键 词：心力衰竭 充血性 干细胞 生长激素(人) 阿霉素 

分 类 号：R686[医药卫生—骨科学]