荔枝核总黄酮对大鼠肝纤维化血小板衍生生长因子、肿瘤坏死因子的影响

Effect of Semen Litchi Total Flavonoids on Platelet-derived Growth Factor and Tumor Necrosis Alpha of Liver Fibrosis Rats

【目的】探讨荔枝核总黄酮(Semen Litchi total flavonoids,SLTF)对二甲基亚硝胺(dimethylnitrosamine,DMN)肝纤维化大鼠血小板衍生生长因子(PDGF)及肿瘤坏死因子(TNF)的影响及其作用机制。【方法】选用SD雄性大鼠60只,随机分为空白组、模型组、水飞蓟宾(SIL)组(50 mg·kg-1·d-1)、SLTF高剂量组(400 mg·kg-1·d-1)、SLTF中剂量组(200mg·kg-1·d-1)、SLTF低剂量组(100 mg·kg-1·d-1)6组。采用DMN腹腔注射制备大鼠肝纤维化模型,造模4周,造模同时给药干预,6周后处死大鼠,观察大鼠肝纤维化水平和肝功能指标,采用放射免疫法测定各组大鼠血清中层粘蛋白(LN)、透明质酸(HA)及Ⅲ型前胶原(PCⅢ)水平,采用苏木精—伊红(HE)染色法和Masson染色观察大鼠肝组织镜下病理变化及纤维化水平,采用PCR法检测各组大鼠肝组织血小板衍生生长因子(PDGF)及肿瘤坏死因子(TNF)mRNA表达水平变化。【结果】HE和Masson染色显示SIL组和SLTF高、中剂量组镜下肝组织纤维化程度较模型组明显降低,肝小叶结构趋于正常;肝功能指标和肝纤3项LN、HA、PCⅢ检测结果显示SIL组和SLTF高、中剂量组肝损伤和肝纤维化程度较模型组和SLTF低剂量组显著减轻;PCR法检测结果显示:SIL组和SLTF高、中剂量组PDGF、TNF-α mRNA表达较模型组显著降低。提示SIL组和SLTF高、中剂量组均有明显的抗大鼠肝纤维化的作用,SLTF高剂量组疗效优于SIL组,差异具有统计学意义(P<0.05);SLTF中剂量组和SIL组疗效相当,差异无统计学意义(P>0.05)。【结论】SLTF可以下调肝纤维化大鼠的PDGF、TNF-α mRNA表达水平,具有一定的抗大鼠肝纤维化作用。

Objective To investigate the effect of Semen Litchi total flavonoids （SLTF） on platelet-derived growth factor （PDGF） and tumor necrosis factor alpha （TNF-α） in rats with liver fibrosis induced by dimethylnitrosamine （DMN）, and to explore its mechanism. Methods Sixty SD male rats were randomly divided into six groups, blank group, model group, silymarin （SIL, 50 mg·kg^-1·d^-1） group, and high-, middle- and low-dose SLTF groups （in the dosage of 400, 200, 100 mg·kg^-1·d^-1, respectively. Rat model of hepatic fibrosis was induced by intraperitoneal injection of DMN for four weeks, and medicine intervention was made at the same time according to the experimental design for six weeks. After treatment, the rats were executed, and we examined the rating of rat hepatic fibrosis and hepatic function indexes, detected serum laminin （LN） , hyaluronic acid （HA） and procollagen type Ⅲ（ PCⅢ） levels, and observed the hepatic pathological changes in liver fibrosis rats under microscope by HE staining and Masson staining. Polymerase chain reaction （PCR） method was used to detect hepatic PDGF and TNF-α mRNA expression levels in all of the groups. Results HE and Masson staining results showed that SIL group and high-, middle-dose SLTF groups had lower microscopically hepatic fibrosis degree than the model group, and their hepatic lobule structure was close to the normal. Serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, LN, HA, and PC m as well as hepatic PDGF and TNF-α mRNA expression levels were decreased in SIL group and high-, middle- dose SLTF groups （P〈0.05 compared with the model group）, and the decrease in high-dose SLTF groups was superior to that in SIL group （P〈0.05） . Middle-dose SLTF group had similar effect to SIL group （P〉0.05） . Conclusion SLTF has certain anti-fibrosis action on liver fibrosis rats through down-regulating the hepatic PDGF and TNF-α mRNA expression levels in liver fibrosis rats.