探讨脐带间充质干细胞（hUC-MSCs）介导HIF-1α/VEGF通路对非酒精性脂肪性肝病（NAFLD）大鼠肝脏损伤的作用。

SD大鼠随机分为正常对照组（NC组）、模型对照组（MC组）和MC+hUC-MSCs组。每组鼠数为7只，分别喂食不同饲料和治疗8周。检测大鼠谷丙转氨酶（ALT）、谷草转氨酶（AST）和胰岛素抵抗指数（HOMA-IR）。光镜观察大鼠肝脏组织病理改变，计算NAFLD活动度积分（NAS）；Western Blot法检测大鼠肝脏组织HIF-?1α和VEGF蛋白表达。组间比较采用单因素方差分析、相关分析选用pearson。

（1）治疗末，NC组ALT、AST和HOMA-IR分别为（41.1±5.9）U/L，（51.7±5.2）U/L，（1.93±0.22）?U/?L低于MC组（153.9±7.1）U/L，（169.8±15.9）U/L，（23.20±2.63）U/L差异具有统计学意义（P?< 0.05）；与MC组比较，MC+hUC-MSCs组大鼠ALT、AST和HOMA-IR降低分别为（90.7±8.1）?U/?L，（110.0±13.1）U/L，（8.43±1.39）U/L差异具有统计学意义（P?< 0.05）。（2）光镜下NC组肝细胞形态正常；MC组肝细胞呈现脂肪变性，较多细胞核变形，肝小叶排列不齐伴炎症细胞浸润；以上肝组织病理改变在MC+hUC-MSCs组明显改善。与NC组比较，MC组大鼠NAS积分增高；与MC组比较，MC+hUC-MSCs组大鼠NAS积分降低[（0.42 ±0.23）分vs （9.15±0.41）?分、（5.15±0.29）分]。（3）Western Blot法检测肝脏组织HIF-1α和VEGF蛋白表达改变：与NC组比较，MC组大鼠HIF-1α和VEGF蛋白表达均增高（P均< 0.05）；与MC组比较，MC+hUC-?MSCs组大鼠HIF-1α和VEGF蛋白表达均降低（P均< 0.05）。单因素相关分析显示大鼠肝脏组织HIF-?1α表达与HOMA-IR指数呈正相关（P均< 0.05）。而且，大鼠肝脏组织NAS评分与肝脏组织HIF-?1α、VEGF表达亦呈正相关（r值分别为0.901、0.874，P均< 0.05）。

?hUC-?MSCs对高糖高脂饲料喂养诱导的NAFLD大鼠受损肝脏功能具有改善作用，其机制与其下调HIF-?1α/?VEGF通路相关。

To evaluate the protective effect of human umbilical cord mesenchymal stem cells on non-alcoholic fatty liver disease and its relationship with HIF-1α/?VEGF mechanism in rats.

Rats were divided randomly into three groups: normal control (NC) , non-alcoholic fatty liver disease model (MC) and hUC-MSCs treatment group (MC+hUC-?MSCs) . The number of each group was eight, the rats of each group were fed different diets and received 8 weeks' intervention. At the end of treatment, ALT, AST and HOMA-IR were measured respectively. The pathologyical changes of liver tissue were observed by light microscope. Then NAS was calculated. The expression of HIF-1α and VEGF protein in liver tissues were detected by Western Blot.

(1) At the end of treatment, compared with the NC group, the values of ALT, AST and HOMA-IR in the MC group were significantly raised (P < 0.05) . MC, ALT, AST and HOMA-?IR were significantly reduced in the MC+hUC-MSCs group. (2) By light microscope: The hepatocyte morphology was normal in NC group. The hepatocyte showed marked steatosis, more nuclear deformation, the lobules were misaligned with inflammatory cell infiltration in the MC group. The above liver histopathological changes were improved in the hUC-MSCs group. Compared with NC group, NAS was increased in the MC group, which could be reversed by hUC-MSCs[ (0.42?± 0.23) vs (9.15±0.41) , (5.15±0.29) ]. (3) Compared with the NC group, the HIF-1α and VEGF protein expression by Western Blot in the liver tissues were significantly raised respectively. Compared with the MC group, the expressions indexes of HIF-1α and VEGF were reversed in the hUC-MSCs group (P < 0.05) . Single factor correlation analysis showed that HIF-1α protein level of of the liver tissues was dependent on HOMA-IR. Further, NAS score was dependent on HIF-1α and VEGF expression (r = 0.901、0.874, P < 0.05) .

Human umbilical cord mesenchymal stem cells can improve liver damage of non-alcoholic fatty liver disease rats. The effects may be related to down regulating HIF-1α /VEGF pathway.