Granulocyte colony-stimulating factors improve myocardial fibrosis in rats with myocardial infarction

doi:10.12307/2022.119

Abstract

Abstract: BACKGROUND: As a powerful stem cell mobilization agent, granulocyte colony-stimulating factor can mobilize bone marrow mesenchymal stem cells to the ischemic area in the early stage of myocardial infarction, regulate extracellular matrix metabolism and inhibit myocardial fibrosis in the early stage of myocardial infarction.
OBJECTIVE: To observe the effect of granulocyte colony-stimulating factor on myocardial fibrosis in rats with acute myocardial infarction.
METHODS: Animal models of acute myocardial infarction were established in rats by coronary artery ligation. After successful modeling, the rats were randomly divided into two groups: model group (n=7) and treatment group (n=7). Another seven rats were randomly selected as blank control group without ligation. At 24 hours after modeling, the treatment group was subcutaneously injected with granulocyte colony-stimulating factor (50 μg/kg/d). Both the model group and the blank control group were injected with the corresponding volume of normal saline at the same site, once a day for 5 days. After 4 weeks, the morphological changes of myocardial tissue were observed by hematoxylin-eosin staining, and the collagen volume fraction was calculated by Masson staining. The levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide were detected by ELISA assay. The protein expressions of matrix metalloproteinase inducer (CD147), matrix metalloproteinase 2 and matrix metalloproteinase inhibitor 2 in the marginal zone of myocardial infarction were detected by immunohistochemistry and western blot.
RESULTS AND CONCLUSION: After 4 weeks, the volume fraction of collagen was significantly higher in the model group than in the blank control group (P < 0.001), the protein levels of CD147 and matrix metalloproteinase 2 were significantly increased (P < 0.001), and the level of matrix metalloproteinase inhibitor 2 protein was significantly decreased. Compared with the model group, the collagen volume fraction in the treatment group decreased significantly (P < 0.001), the protein levels of CD147 and matrix metalloproteinase 2 decreased (P < 0.001), and the level of matrix metalloproteinase inhibitor 2 protein increased significantly (P < 0.001). Compared with the blank control group, the expression levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide significantly increased in the treatment group (P < 0.001). Compared with the model group, the expression levels of serum type I procollagen carboxyl terminal peptide and type III procollagen N-terminal peptide reduced significantly in the treatment group (P < 0.001). To conclude, granulocyte colony-stimulating factor can improve myocardial fibrosis in rats with acute myocardial infarction, probably by down-regulating the expression of CD147 protein, directly or indirectly regulating the balance of matrix metalloproteinase 2/matrix metalloproteinase inhibitor 2 ratio, improving extracellular matrix metabolism and inhibiting collagen deposition.

Key words: myocardial infarction, myocardial fibrosis, granulocyte colony-stimulating factor, CD147, matrix metalloproteinase 2, matrix metalloproteinase inhibitor 2

CLC Number:

Yin Tingting, Du Dayong, Jiang Zhixin, Liu Yang, Liu Qilin, Li Yuntian. Granulocyte colony-stimulating factors improve myocardial fibrosis in rats with myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(5): 730-735.

Figures/Tables 7

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