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目的构建RGD环肽修饰纳米脂质体(cRGD-NL),利用其包封氧化苦参碱(OM),比较单纯低浓度OM(2 mg/kg体质量,2次/周)和含相应量OM的携OM纳米脂质体(NL-OM)或携OM环肽修饰纳米脂质体(cRGD-NL-OM)对大鼠四氯化碳(CCl4)肝纤维化影响,明确cRGD-NL-OM能否有效降低OM抗肝纤维化有效剂量和用药频次。方法 SD大鼠分6组(每组8只):正常对照组、模型(CCl4)组、单纯NL干预(CCl4+NL)组、单纯OM干预(CCl4+OM)组、NL-OM干预(CCl4+NL-OM)组和cRGD-NL-OM干预(CCl4+cRGD-NL-OM)组。各组按OM 2 mg/kg体质量、每周2次药量于造模4周后给予相应药物或容媒,给药4周后处死动物,采集血清和肝组织标本。HE和Masson染色观察病理学组织变化,生化分析或ELISA检测血清肝功能胶原代谢变化;荧光定量PCR检测Ⅰ型胶原α2链(COL1A2)mRNA水平;免疫印记法检测α-平滑肌肌动蛋白(α-SMA)表达。结果 与模型组相比,cRGD-NL-OM组和NL-OM组大鼠血清学指标及肝组织病理学改善显著,同时COL1A2 mRNA水平及α-SMA表达显著下降,且cRGD-NL-OM较NL-OM组改善更为明显。相反,单纯NL组及单纯OM组各项指标与模型组相比无显著差异。结论 cRGD-NL-OM显著降低OM抗大鼠肝纤维化有效剂量与用药频次,该新剂型有重要的临床应用前景。
OBJECTIVE: To construct the RGD cyclic peptide modified liposomes (cRGD-NL) and encapsulate oxymatrine (OM). Compare with low concentration OM (2 mg / kg body weight twice daily) The effect of NL-OM or cRGD-NL-OM on hepatic fibrosis induced by carbon tetrachloride (CCl4) in rats was studied. The expression of cRGD-NL- OM can effectively reduce OM anti-liver fibrosis effective dose and frequency of medication. Methods SD rats were divided into 6 groups (n = 8): normal control group, CCl4 group, CCl4 + NL group, CCl4 + OM group and CCl4 + NL-OM group and cRGD-NL-OM intervention group (CCl4 + cRGD-NL-OM). Each group was given OM 2 mg / kg body weight twice a week dose 4 weeks after the model was given the appropriate drug or bulk media, 4 weeks after administration of animals were sacrificed, serum and liver tissue samples were collected. The pathological changes were observed by HE and Masson staining, and the changes of serum hepatic collagen were detected by biochemical analysis or ELISA. The mRNA level of α1 chain (COL1A2) was detected by fluorescence quantitative PCR and the expression of α-smooth muscle actin (α- SMA) expression. Results Compared with the model group, the serological parameters and hepatic histopathology of rats in cRGD-NL-OM group and NL-OM group were significantly improved. Meanwhile, the expression of COL1A2 mRNA and α-SMA were significantly decreased, while cRGD-NL-OM NL-OM group to improve more obvious. In contrast, there was no significant difference in the indexes of NL group and OM group alone compared with model group. Conclusion cRGD-NL-OM significantly reduces the effective dose and frequency of OM against rat liver fibrosis. The new dosage form has important clinical application prospects.