Abstract:

BACKGROUND: RhoA kinase inhibitor Fasudil can effectively suppress cardiac hypertrophy following myocardial infarction.
OBJECTIVE: To observe the effects of Fasudil combined with bone marrow mesenchymal stem cell (BMSC) transplantation on cardiac function in rat models of acute myocardial infarction (AMI), and to investigate the synergetic therapeutic effects of Fasudil and BMSC transplantation.
METHODS: BMSCs were incubated and amplified in Sprague Dawley rats in vitro. An additional 42 adult female Sprague Dawley rats were selected to ligate the anterior descending branch to establish models of AMI. These rats were randomly assigned to three groups. BMSCs were injected into rats in the BMSC transplantation group. BMSC transplantation and Fasudil treatment were performed in BMSC transplantation + Fasudil group. Rats in the myocardial infarction group were left intact. Four weeks post-transplantation, two-dimensional echocardiography was used to detect cardiac function. SRY-PCR was used to detect the SRY gene which is a specific marker of Y chromosome. Western blot assay was utilized to detect RhoA protein expression, and the pathology was checked.
RESULTS AND CONCLUSION: Compared with myocardial infarction group, left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly decreased in the BMSC transplantation group and BMSC transplantation + Fasudil group (P < 0.01), but ejection fraction was significantly increased (P < 0.01). The changes were better in BMSC transplantation + Fasudil group compared with BMSC transplantation group (P < 0.05). The SRY expression was determined in BMSC transplantation group and BMSC transplantation + Fasudil group, but no SRY gene was detected in myocardial infarction group. The protein expression level of RhoA significantly decreased in BMSC transplantation + Fasudil group than in myocardial infarction group and BMSC transplantation group (P < 0.05). Myocardial repair was better in the BMSC transplantation group and BMSC transplantation + Fasudil group than in the myocardial infarction group, and it was significant in the BMSC transplantation + Fasudil group than in the BMSC transplantation group. Results have indicated that BMSC transplantation alone, BMSC transplantation combined with Fasudil can improve cardiac function of AMI rats, and decrease the extent of ventricular dilation. Their combination has an optimal effect, with synergetic therapeutic effects on myocardial infarction.