黄芪多糖-冬虫夏草多糖合剂抑制大鼠动脉移植慢性排斥反应的实验研究

Effects of Astragalus polysaccharides and Cordyceps sinensis mycelium mixture on the transforming growth factor-β_1 expression in chronic rejection of artery transplantation:experiment with rats

目的观察黄芪多糖-冬虫夏草多糖合剂对大鼠腹主动脉移植慢性排斥反应的影响。方法建立大鼠腹主动脉移植模型,移植后大鼠随机分为对照组、霉酚酸酯(MMF)组、黄芪多糖(APS)组和黄芪多糖-冬虫夏草多糖合剂(APS-CPS)组,同时设立假手术组。各组动物在饲养35 d后,观察移植动脉的病理变化,分别用免疫组织化学和胶原纤维染色,观察移植动脉 TGF-β_1的表达、胶原蛋白合成;应用流式细胞术榆测脾脏中 CD4^+、CD8^+阳性 T 淋巴细胞。结果对照组血管内膜明显增厚,平滑肌细胞明显增生,胶原纤维增生明显;TGF-β_1蛋白于内膜平滑肌细胞、单核细胞、动脉内皮细胞等均呈阳性表达。APS-CPS 组血管壁三层结构清晰,内膜未见明显增牛,胶原原纤维稀疏;TGF-β_1表达较对照组明显减弱(P<0.01),且移植前后 CD4^+、CD8^+阳性 T 淋巴细胞百分率、CD4^+/CD8^+比值均无明显变化(P>0.05)。结论 APS-CPS 抑制大鼠动脉移植慢性排斥反应,能下调 TGF-β_1表达,抑制内膜平滑肌细胞增殖及胶原蛋白合成,维持 CD4^+/CD8^+比值的正常。

Objective To explore the effect of Astragalus polysaccharides （APS） and Cordyceps sinensis （CP） mycelium mixture on the chronic rejection of artery transplantation. Methods The abdominal arteries of 180 Wister rats were isolated and transplanted to 180 SD rats whose with their abdominal arteries resected. The 180 recipient SD rats were randomly divided into blank control group （n = 20）, APS group （n =40, receiving gastric perfusion ofAPS 1 mg/kg bid）, APS ＋low-dose CP group （n = 40, receiving APS and CP mycelium powder 1.25 g/d ）, APS ＋ medium-dose CP group （ n = 40, receiving APS and CP mycelium powder 2.5 g/d ） , and APS ＋ high-dose CP group （n = 40, receiving APS and CP mycelium powder 5 g/d ）. Thirty days later the SD rats were killed with the transplanted abdominal arteries taken out to undergo microscopy. The expression of transforming growth factor （TGF）-β1 in the transplanted artery was examined by immunohistoehemistry. Results In the control group, overexpression of TGF-β1 was observed in the intimal smooth muscle cells, monocytes, arterial endothelial cells, and arteriole, venule, and blood capillary endothelial cells in extima. However, the expression levels of TGF-β1 in the APS group and the 3 mixture administration groups were all significantly lower, especially in the medium- and high-dose groups （all P 〈 0. Ol ）. Severe edema of arterial endothelial cells and proliferation of monocytes were observed microscopically in the control group. Under electron microscope, rough endoplasmic reticulum and Golgi body were abundant in the control group. While in the mixture administration groups these changes were either weakened or absent. Conclusion Astragalus polysaccharides and Cordyceps sinensis mycelium polysaceharides mixture can decrease the expression of TGF-β1 and inhibit the synthesis of collagen in the transplanted arteries.