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胎盘提取物促进 CCl4 损伤肝大鼠模型的肝再生。

Placenta extract promote liver regeneration in CCl4-injured liver rat model.

机构信息

Department of Biomedical Science, CHA University, Seoul, Republic of Korea.

出版信息

Int Immunopharmacol. 2011 Aug;11(8):976-84. doi: 10.1016/j.intimp.2011.02.012. Epub 2011 Feb 24.

DOI:10.1016/j.intimp.2011.02.012
PMID:21354355
Abstract

The human placenta is an organ for fetus development and abundant reservoir of various bioactive molecules. Interest to human placenta extract (hPE) is growing, and application with trial of hPE is widening in oriental medicine including in liver diseases. However, underlying mechanisms for therapeutic effects are still unclear. Here, we investigated therapeutic effects of hPE in carbon tetrachloride (CCl(4))-injured rat liver model in vivo and in damaged rat hepatic cells exposed to CCl(4) in vitro. In addition, regulation of inflammatory responses by treatment of hPE was investigated. Serum levels of GOT/AST and GPT/ALT were significantly reduced (P<0.05), and uptake/excretion of indocyanine green in serum was significantly induced at 3 weeks after intravenous hPE administration in CCl(4)-injured rat model (P<0.05). Expression of type I collagen (Col I) and α-smooth muscle actin (α-SMA) was decreased, whereas that of matrix metalloproteinase-9 (MMP-9) was increased resulting in improvement of score for fibrotic grade in hPE group. Also, albumin, proliferation activities and molecules associated with liver regeneration (e.g. interleukin-6, gp130, ATP binding cassette transporters, cyclin A) were more increased in hPE administration group than Non-hPE group. hPE administration suppressed activated T-cell proliferation via increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines. These results suggest that hPE could be effective for liver disease through reduction of fibrosis, induction of liver regeneration, and regulation of inflammatory responses. These findings are important for understanding the roles of hPE and provide evidences for therapeutic effects of hPE in hepatic diseases which could lead to potential clinical applications.

摘要

人胎盘是胎儿发育的器官,也是各种生物活性分子的丰富储存库。对人胎盘提取物(hPE)的兴趣日益增加,其在东方医学中的应用也在扩大,包括肝脏疾病。然而,其治疗效果的潜在机制尚不清楚。在这里,我们研究了 hPE 在体内四氯化碳(CCl(4))损伤大鼠肝模型和体外暴露于 CCl(4)的受损大鼠肝细胞中的治疗作用。此外,还研究了 hPE 对炎症反应的调节作用。静脉注射 hPE 3 周后,CCl(4)损伤大鼠模型血清 GOT/AST 和 GPT/ALT 水平显著降低(P<0.05),血清吲哚菁绿摄取/排泄明显增加(P<0.05)。I 型胶原(Col I)和α-平滑肌肌动蛋白(α-SMA)的表达减少,而基质金属蛋白酶-9(MMP-9)的表达增加,导致 hPE 组纤维化程度评分改善。此外,白蛋白、增殖活性和与肝再生相关的分子(如白细胞介素-6、gp130、ATP 结合盒转运蛋白、细胞周期蛋白 A)在 hPE 给药组中的增加多于非 hPE 组。hPE 给药通过增加抗炎细胞因子和减少促炎细胞因子来抑制活化 T 细胞增殖。这些结果表明,hPE 可通过减少纤维化、诱导肝再生和调节炎症反应,对肝脏疾病有效。这些发现对于理解 hPE 的作用很重要,并为 hPE 在肝脏疾病中的治疗效果提供了证据,这可能导致潜在的临床应用。

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