[Therapeutic effects of recombinant human growth hormone and mesenchymal stem cells transplantation alone or in combination in adriamycin induced cardiomyopathy rat model].
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 x 10(6)/100 microl, 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) microg/L, (2.48 +/- 0.90) vs (1.25 +/- 0.42) microg/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.
Li
Yan-Hong
YH
Department of Cardiology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Wang
Feng-Zhi
FZ
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000628:therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin; D006333:Heart Failure / Q000139:chemically induced / Q000628:therapy*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D004317:Doxorubicin