基于蛋白质组学探讨益肝化瘀方改善肝纤维化的机制 点击下载
| 论文标题： | 基于蛋白质组学探讨益肝化瘀方改善肝纤维化的机制 |
| 英文标题： | |
| 中文摘要： | 目的 探讨益肝化瘀方改善小鼠肝纤维化的作用及机制。方法将小鼠随机分为空白组（生理盐水）、模型组（生理盐水）和益肝化瘀方低、高剂量组（28.98、57.96g/kg，以生药量计），每组8只。除空白组外，其余各组均腹腔注射15%四氯化碳橄榄油溶液建立肝纤维化模型。自造模第3周起，每天灌胃给药/生理盐水1次，连续4周。末次给药后，计算肝脏指数，检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性及肝组织中羟脯氨酸（HYP）含量；评估肝组织病理学变化；基于蛋白质组学分析肝组织中差异表达蛋白，对其进行生物信息学分析，并利用蛋白免疫印迹（WB）法及免疫组化（IHC）法验证核心差异蛋白的表达情况。结果与空白组相比，模型组小鼠肝脏指数以及血清中ALT、AST活性和肝组织中HYP含量均显著升高（P＜0.05），肝组织出现明显病理损伤及胶原纤维沉积。与模型组相比，益肝化瘀方高剂量组小鼠上述指标均显著降低（P＜0.05），肝脏病理损伤及胶原纤维沉积明显改善。在模型组与益肝化瘀方高剂量组中，共筛选出210个差异蛋白；差异蛋白显著富集于细胞外基质（ECM）-受体相互作用、脂质代谢等通路。WB法及IHC法检测结果表明，益肝化瘀方能显著抑制模型小鼠肝组织中异常升高的Ⅳ型胶原α1链（COL4A1）、富含半胱氨酸的酸性分泌蛋白（SPARC）、玻连蛋白（VTN）和层粘连蛋白亚基α5（LAMA5）的表达（P＜0.05）。结论益肝化瘀方可能通过抑制COL4A1、LAMA5、SPARC及VTN等蛋白的表达，从而阻断ECM-受体相互作用通路，进而抑制ECM的过度沉积与基底膜重构，最终发挥抗肝纤维化作用。 |
| 英文摘要： | OBJECTIVE To investigate the effects and mechanism of Yigan huayu formula in alleviating liver fibrosis in mice. METHODS Mice were randomly divided into blank group （normal saline）， model group （normal saline）， Yigan huayu formula low- and high-dose groups （28.98， 57.96 g/kg， calculated by crude drug）， with 8 mice in each group. Except for the blank group， the liver fibrosis model was induced by intraperitoneal injection of 15%CCl 4 -olive oil solution. From the third week， the mice received the medicine/normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， liver indexes were calculated， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， as well as the hydroxyproline （HYP） content in liver tissue， were measured. Liver histopathology was evaluated. Differentially expressed proteins （DEPs） in liver tissue were analyzed based on proteomics， followed by bioinfo rmatics analysis. The expressions of core DEPs were validated using Western blot （WB） and immunohistochemistry （IHC） methods. RESULTS Compared with the blank group， the model group showed significantly elevated liver indexes， serum activities of ALT and AST， and hepatic HYP content （ P ＜0.05）， along with obvious pathological damage and collagen deposition. Compared with the model group， the above indexes of mice in the Yigan huayu formula high-dose group were decreased significantly （ P ＜0.05）， with marked improvement in liver pathological damage and collagen deposition. Proteomics identified 210 DEPs between the model group and Yigan huayu formula high-dose group. DEPs were significantly enriched in extracellular matrix （ECM）-receptor interaction and lipid metabolism pathways. WB and IHC confirmed that Yigan huayu formula could significantly inhibit the abnormally elevated expressions of collagen type Ⅳ alpha1 chain （COL4A1）， secreted protein acidic and rich in cysteine （SPARC）， vitronectin （VTN） and laminin subunit alpha5 （LAMA5） in liver tissue of mice （ P ＜0.05）. CONCLUSIONS Yigan huayu formula may exert anti-hepatic fibrosis effects by inhibiting the expressions of proteins such as COL4A1， LAMA5， SPARC， and VTN， thereby blocking the ECM-receptor interaction signaling pathway， and subsequently suppressing excessive ECM deposition and basement membrane remodeling. |
| 期刊： | 2026年第37卷第09期 |
| 作者： | 王聪慧；马贵萍；王龙珠；卢芬萍；李艳芳；葛秋寒；胡世平 |
| 英文作者： | WANG Conghui，MA Guiping，WANG Longzhu，LU Fenping，LI Yanfang，GE Qiuhan，HU Shiping |
| 关键字： | 益肝化瘀方；肝纤维化；蛋白质组学；ECM-受体相互作用；生物机制 |
| KEYWORDS： | Yigan huayu formula； liver fibrosis； proteomics； ECM-receptor interaction； biological mechanism |
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