【目的】 观察肉桂醛对非酒精性脂肪肝（NAFLD）大鼠肝纤维化的治疗作用及机制。【方法】 采用高脂饲料喂养法构建 NAFLD大鼠模型。将造模成功的大鼠随机分为模型组，肉桂醛低、高剂量组及肉桂醛高剂量+K6PC-5[鞘氨醇激酶1（SphK1） 激活剂]组，另取健康大鼠作为正常组。分组干预后，应用全自动生化分析仪检测血脂[总胆固醇（TC）、甘油三酯（TG）、低密 度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]水平及肝功能[丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶 （AST）]，酶联免疫吸附分析（ELISA）检测血清炎性因子肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、干扰素γ（IFN-γ）水 平，苏木精-伊红（HE）染色法观察肝组织病理形态，Masson染色法观察肝纤维化程度，免疫组织化学法检测纤维化相关蛋白 Ⅰ型胶原α1（COL1A1）、α-平滑肌肌动蛋白（α-SMA）表达，蛋白免疫印迹（Western Blot）法检测肝组织SphK1、鞘氨醇-1-磷 酸（S1P）蛋白表达。【结果】 与正常组比较，模型组肝小叶结构破坏，肝细胞肿胀变性，排列紊乱，胞质内产生大量脂肪空泡， 炎性细胞浸润明显，蓝色胶原纤维大量沉积，纤维化程度严重，TC、 TG、 LDL-C，ALT、AST，TNF-α、 IL-6、IFN-γ等水 平及COL1A1、a-SMA，SphK1、S1P表达水平升高，HDL-C水平降低，差异均有统计学意义（P＜0.05）；与模型组比较，肉 桂醛低、高剂量组肝组织病理改变减轻，蓝色胶原纤维沉积相对减少，纤维化程度减轻，TC、TG、LDL-C，ALT、AST， TNF-α、IL-6、IFN-γ等水平及COL1A1、a-SMA表达，SphK1、S1P表达水平降低，HDL-C水平升高，差异均有统计学意义 （P＜0.05）；与肉桂醛高剂量组比较，肉桂醛高剂量+K6PC-5组肝小叶结构破坏严重，肝细胞肿胀变性严重，胞质内脂肪空 泡剧增，炎性细胞浸润明显，蓝色胶原纤维沉积增多，纤维化程度加重，TC、TG、LDL-C，ALT、AST，TNF-α、IL-6、 IFN-γ 等水平及 COL1A1、a-SMA，SphK1、S1P 表达水平升高，HDL-C 水平降低，差异均有统计学意义（P＜0.05）。 【结论】 肉桂醛可改善NAFLD大鼠肝纤维化，其作用机制与抑制SphK1/S1P信号通路有关。

Objective To investigate the therapeutic effects and mechanisms of cinnamaldehyde （CA） on hepatic fibrosis in non-alcoholic fatty liver disease （NAFLD） rats. Methods A NAFLD rat model was established using a high-fat diet. Successfully modeled rats were randomly divided into： model group， low- and high-dose CA groups， and high-dose CA +K6PC-5 [a sphingosine kinase-1（SphK1） activator] group， with healthy rats as normal controls. After intervention，serum lipid profiles [total cholesterol （TC），triglycerides （TG），low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and liver function markers [alanine aminotransferase （ALT）， aspartate aminotransferase （AST）] were measured using an automated biochemical analyzer. Serum inflammatory cytokines （TNF-α，IL-6，IFN-γ） were quantified by ELISA. Hepatic histopathology was evaluated via hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry detected fibrosis-related proteins （COL1A1，α-SMA），while Western Blot analyzed SphK1 and sphingosine-1-phosphate （S1P） expression. Results Compared with the normal group，the model group showed significant destruction of hepatic lobule structure， hepatocyte swelling and degeneration， disordered cell arrangement， abundant lipid vacuoles in cytoplasm， obvious inflammatory cell infiltration， extensive blue collagen fiber deposition， and severe fibrosis. Moreover，the levels of TC，TG，LDL-C，ALT，AST，TNF-α，IL-6，IFN-γ，COL1A1， α-SMA，SphK1，and S1P were significantly increased，while HDL-C levels were decreased，with statistically significance （P＜0.05）. Compared with the model group， both low- and high-dose CA groups demonstrated alleviated liver histopathological changes，reduced blue collagen fiber deposition，and improved fibrosis. These groups also showed significantly decreased levels of TC，TG，LDL-C，ALT，AST，TNF-α，IL-6，IFN-γ， COL1A1，α-SMA，SphK1，and S1P，along with increased HDL-C levels （P＜0.05）. However，compared with the high-dose CA group，the high-dose CA + K6PC-5 group exhibited more severe destruction of hepatic lobule structure，aggravated hepatocyte swelling and degeneration，dramatically increased cytoplasmic lipid vacuoles， significant inflammatory cell infiltration， increased blue collagen fiber deposition， and worsened fibrosis. This group also had significantly elevated levels of TC， TG， LDL-C， ALT， AST， TNF- α， IL-6， IFN- γ， COL1A1，α-SMA，SphK1，and S1P，along with reduced HDL-C levels （P＜0.05）.Conclusion CA alleviates hepatic fibrosis in NAFLD rats by inhibiting the SphK1/S1P signaling pathway.

R285.5

武汉市医学科研项目（编号：WX20Z21）