沙利度胺治疗改善胆汁性肝硬化大鼠肝肺综合征  

Thalidomide treatment ameliorates hepatopulmonary syndrome in rats with biliary cirrhosis

作　　者：江丽萍 江晓燕 王洪燕 吴文杰 欧旸 陈明胜 JIANG Li-ping;JIANG Xiao-yan;WANG Hong-yan;WU Wen-jie;OU Yang;CHEN Ming-sheng(Department of General Medicine,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350001,China)

机构地区：[1]福建医科大学孟超肝胆医院综合内科,福州350001

出　　处：《肝脏》2023年第2期175-180,共6页Chinese Hepatology

基　　金：福建省自然科学基金项目(2020J011170)。

摘　　要：目的 研究沙利度胺治疗肝肺综合征的机制。方法 采用胆总管结扎术诱导大鼠肝肺综合征(HPS)。术后4周开始沙利度胺(实验组)或蒸馏水(对照组)100 mg/(kg·d)治疗2周。对所有大鼠进行生化、血浆及肺泡灌洗液血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)测定和血气分析。取大鼠肝脏进行组织病理学检查,肺组织进行实时荧光定量PCR和Western blot分析。在另外一个平行组中,确定了模型制备成功。结果 沙利度胺治疗后肺泡-动脉血氧分压(A-aPO2)和血清VEGF、TNF-α水平明显降低[沙利度胺治疗组大鼠A-aPO2秩为25.10(10),对照组为15.60(10)(P<0.001);沙利度胺治疗组大鼠血清VEGF水平秩为25.50(10),对照组为14.50(10)(P<0.001);沙利度胺治疗组大鼠血清TNF-α水平秩为25.50(10);对照组为12.60(10)(P<0.001)]。同时,沙利度胺可降低肺VEGF、VEGF受体2(VEGFR-2)的mRNA[VEGF模型组VS沙利度胺组:23.25(10)vs 15.10(10);VEGFR-2模型组VS沙利度胺组:22.40(10)VS 15.60(10)]和蛋白[VEGF模型组VS沙利度胺组:2.03±0.96 vs 1.45±0.99;VEGFR-2模型组VS沙利度胺组:21.50(10)VS 12.25(10)]的表达(P均<0.05)。结论 沙利度胺可降低胆总管结扎大鼠A-aPO2,提示沙利度胺可改善该实验动物模型的HPS。其作用机制可能与抑制TNF-α,从而抑制VEGF/VEGFR-2通路,减少肺内血管生成有关。Objective To investigate the mechanism of thalidomide in the treatment of hepatopulmonary syndrome(HPS). Methods Common bile duct ligation was used to induce HPS in rats. Four weeks after operation, experimental group was treated by thalidomide [100 mg/(kg·d)], control group was treated by distilled water [100 mg/(kg·d)] for 2 weeks. Biochemical, plasma and bronchoalveolar lavage fluid vascular endothelial growth factor(VEGF), TNF-α and blood gas analysis were performed in all rats. The rat liver was collected for histopathological examination, and the lung tissue was analyzed by real-time fluorescence quantitative PCR and western blot. In another parallel group, the results showed that the model was successful. Results After thalidomide treatment, the alveolar-arterial partial pressure of oxygen(A-aPO2) and the levels of serum VEGF and TNF-α were significantly decreased [A-aPO2rank was 25.10(10) in thalidomide group, 15.60(10) in control group(P<0.001), 25.50(10) in thalidomide group, 14.50(10) in control group(P<0.001). serum TNF-α level was 25.50(10) in thalidomide treatment group, and 12.60(10) in control group(P<0.001)]. Meanwhile, thalidomide decreased lung VEGF, VEGF receptor 2(VEGFR-2) mRNA [VEGF model group vs. thalidomide group: 23.25(10) vs. 15.10(10);VEGFR-2 model group vs. thalidomide group: 22.40(10) vs. 15.60(10)] and protein [VEGF model group vs. thalidomide thalidomide group: 2.03±0.96 vs. 1.45±0.99;VEGFR-2 model group vs. thalidomide group: 21.50(10) vs. 12.25(10)] expression(all P<0.05). Conclusion Thalidomide can reduce Amura PO2in choledochal ligation rats, suggesting that thalidomide can improve the HPS of experimental animal model. The mechanism may be related to the inhibition of TNF-α, to inhibit VEGF/VEGFR-2 pathway and reduce pulmonary angiogenesis.

关 键 词：沙利度胺 肝肺综合征 胆汁性肝硬化 血管内皮生长因子 肿瘤坏死因子 

分 类 号：R575.2[医药卫生—消化系统] R563[医药卫生—内科学]