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目的:从噬菌体随机肽库中筛选血小板衍生生长因子受体β链(PDGF-Rβ)的亲和短肽并探讨其对CCl4诱导的肝纤维化模型中的抗肝纤维化作用。方法:以重组可溶性人PDGF-Rβ作为靶标,应用噬菌体随机十二肽库进行筛选,经过3轮淘选,提取阳性噬菌体克隆ssDNA,测序并进行序列分析,选择其中出现频率高的展示肽,并根据其氨基酸序列人工合成亲和短肽,应用亲和短肽实施抗肝纤维化试验,设亲和短肽C1组亲和短肽C2组,秋水仙碱组,模型组,空白组,造模五周后处死采血,通过分析肝脏中的HPY水平并对肝脏进行病理组织学检查,检测其抗肝纤维化的作用。结果:人工合成的亲和肽PDGF-RβC1用于抗肝纤维化治疗能减轻炎症,减少胶原纤维形成,ALT羟脯氨酸与肝纤维化小鼠模型组相比差异具有统计学意义(P<0.05)。结论:通过噬菌体肽库技术能筛选出与PDGF-Rβ结合的噬菌体展示肽可以改善实验性肝纤维化小鼠的肝脏组织结构和肝功能。
OBJECTIVE: To screen short peptides derived from platelet-derived growth factor receptor β chain (PDGF-Rβ) from phage random peptide library and investigate its anti-hepatic fibrosis effect in CCl4-induced hepatic fibrosis model. Methods: Recombinant soluble human PDGF-Rβ was used as a target and phage was randomly selected for screening. After 3 rounds of panning, positive phage cloned ssDNA was extracted, sequenced and sequenced. According to its amino acid sequence, synthetic affinity short peptide was synthesized, and anti-liver fibrosis test was carried out by using affinity short peptide. The affinity peptide short peptide C2 group, the colchicine group, the model group, the blank group, Blood was sacrificed five weeks later, and the hepatic fibrosis was examined by analyzing the level of HPY in the liver and performing histopathological examination on the liver. Results: The synthetic peptide PDGF-RβC1 could inhibit the inflammation and reduce the formation of collagen fibers in the treatment of hepatic fibrosis. The difference between the ALT group and the liver fibrosis model group was statistically significant (P < 0.05). Conclusion: The phage displayed peptides binding with PDGF-Rβ can be used to improve the liver tissue structure and liver function of experimental hepatic fibrosis mice by phage peptide library technology.