Effects of icariin combined with injectable chitosan/collagen composite hydrogel on angiogenesis in rats with myocardial infarction

doi:10.12307/2023.550

Abstract

Abstract: BACKGROUND: Icariin can be used in the treatment of cardiovascular diseases, however, its high lipid solubility, poor water solubility, and obvious hepatic first-pass effect result in low bioavailability, which limits its clinical application.
OBJECTIVE: To observe the effects of icariin combined with injectable chitosan/collagen composite hydrogel on myocardial infarction in rats.
METHODS: Chitosan/collagen composite hydrogels loaded with different concentrations (0.4, 0.8, and 1.6 mg/mL) of icariin were prepared and marked as CS/COI/ICA0.4, CS/COI/ICA0.8, and CS/COI/ICA1.6, respectively. The cytocompatibility and sustained release performance of the hydrogels were tested. The left anterior descending artery of adult SD rats was ligated to establish a myocardial infarction model. Ninety-six myocardial infarction rat models were randomly divided into four groups (24 rats in each group): model, CS/COI/ICA0.4, CS/COI/ICA0.8, and CS/COI/ICA1.6 groups, and the infarct area, peri-infarct area and posterior wall area of rats in these four groups were injected with PBS or hydrogels. Normal rats were selected as normal controls. The experimental parameters were measured after 28 days of treatment.
RESULTS AND CONCLUSION: (1) In vitro cell experiments showed that chitosan/collagen composite hydrogels loaded with different concentrations of icariin had good cytocompatibility, which was beneficial to the proliferation and survival of cardiomyocytes. The release of icariin from all the three hydrogels kept for more than 32 days. (2) The animal experiments showed that the cardiac structure of rats in the model group was severely remodeled and the cardiac function was significantly decreased compared with the normal control group (P < 0.01). The CS/COI/ICA0.4, CS/COI/ICA0.8, and CS/COI/ICA1.6 groups had a significant improvement in cardiac structure and cardiac function compared with the model control group (P < 0.05), with the most significant improvement in the CS/COI/ICA1.6 group (P < 0.05). Masson staining showed that the degree of myocardial fibrosis in the CS/COI/ICA0.4, CS/COI/ICA0.8, and CS/COI/ICA1.6 groups was significantly less (P < 0.05), while the thickness of ventricular wall was significantly greater compared with that in the model group (P < 0.05). Immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction showed that the immunoreactivities of CD31 and α-smooth muscle actin and mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor were significantly decreased compared with the normal control group (all P < 0.05), while those were significantly increased in the CS/COI/ICA0.4, CS/COI/ICA0.8, and CS/COI/ICA1.6 groups compared with the model group (all P < 0.05). (3) These findings suggest that chitosan/collagen/icaricin composite hydrogels can stimulate angiogenesis by increasing the expression of vascular endothelial growth factor and basic fibroblast growth factor in myocardial tissues in infracted areas to improve the local microenvironment of myocardial tissue due to insufficient perfusion, thereby inhibiting ventricular remodeling and improving cardiac function.

Key words: myocardial infarction, icariin, chitosan, collagen, hydrogel, angiogenesis

CLC Number:

He Wenfeng, Xue Cheng, Zheng Jiankang, Shuai Zhuang, Yue Rongchuan. Effects of icariin combined with injectable chitosan/collagen composite hydrogel on angiogenesis in rats with myocardial infarction[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(25): 3992-3998.

Figures/Tables 10

5组大鼠心率、左室后壁舒张末期厚度比较差异无显著性意义(P > 0.05)。与正常对照组比较，模型对照组大鼠的每搏输出量、射血分数、短轴缩短率、心输出量明显减少(P < 0.05)，左室前壁收缩末期厚度、左室前壁舒张末期厚度、左室后壁收缩末期厚度减少(P < 0.05)，左室收缩末期内径、左室舒张末期内径、左室收缩末期容积、左室舒张末期容积增加(P < 0.05)。与模型对照组比较，CS/COI/ICA0.4组、CS/COI/ICA0.8组、CS/COI/ICA1.6组大鼠的每搏输出量、射血分数、短轴缩短率、心输出量明显增加(P < 0.05)，左室前壁收缩末期厚度、左室前壁舒张末期厚度、左室后壁收缩末期厚度增加(P < 0.05)，左室收缩末期内径、左室舒张末期内径、左室收缩末期容积、左室舒张末期容积减少(P < 0.05)。与CS/COI/ICA0.4组、CS/COI/ICA0.8组比较，CS/COI/ICA1.6组大鼠的每搏输出量、射血分数、短轴缩短率、心输出量明显增加(P < 0.05)，左室前壁收缩末期厚度、左室前壁舒张末期厚度、左室后壁收缩末期厚度增加(P < 0.05)，左室收缩末期内径、左室舒张末期内径、左室收缩末期容积、左室舒张末期容积减少(P < 0.05)。 2.4.2 Masson三色染色由图5可见，模型对照组梗死部位可见广泛的胶原沉积与严重的心室扩张，心室壁较薄；相较于模型对照组，CS/COI/ICA0.4组、CS/COI/ICA0.8组、CS/COI/ICA1.6组梗死部位胶原沉积减少、心室扩张减轻、心室壁增厚，其中以CS/COI/ICA1.6组改善最明显。利用Image J软件定量分析心肌纤维化面积与左心室壁厚度，得出以下结果：CS/COI/ICA0.4组、CS/COI/ICA0.8组、CS/COI/ICA1.6组心肌纤维化面积少于模型对照组(P < 0.05)，心室壁厚度大于模型对照组(P < 0.05)；CS/COI/ICA0.8组心肌纤维化面积少于CS/COI/ICA0.4组(P < 0.05)，心室壁厚度大于CS/COI/ICA0.4组(P < 0.05)；CS/COI/ICA1.6组心肌纤维化面积少于CS/COI/ICA0.8组(P < 0.05)，心室壁厚度大于CS/COI/ICA0.8组(P < 0.05)，见表5。"

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