姜黄素衍生物对实验性非酒精性脂肪性肝炎的治疗作用

The effects of curcumin derivative on experimental steatohepatitis

目的观察姜黄素衍生物对实验性非酒精性脂肪性肝炎（NASH）的治疗作用。方法60只雄性SD大鼠随机分为正常组、模型组、等渗盐水对照组（等渗盐水组）、姜黄素灌胃组（姜黄素组）、姜黄素衍生物静脉注射组（衍生物组），每组12只。通过高脂饲料结合四氯化碳的复合方式建立大鼠NASH模型。造模后分别给予姜黄衍生物尾静脉注射及姜黄素灌胃治疗（剂量50mg／kg），等渗盐水作为对照。治疗结束后取血及肝组织，计算肝指数，进行血脂和肝功能指标检测及病理组织学检查。RT-PCR法检测肝组织中肿瘤坏死因子α（TNFα、核转录因子κB（NF-κB）、羟甲戊二单酰辅酶A（HMG-CoA）还原酶的mRNA转录水平，Westernblot检测TNFa及NF-KB的蛋白质表达水平。多组计量资料比较采用成组设计的方差分析、Kruskal-WallisH检验，两两比较采用LSD法、成组设计的Wilcoxon秩和检验，P〈0．05为差异有统计学意义。结果与等渗盐水组比较，衍生物组大鼠血清ALT、AST和总胆固醇水平明显下降[分别为（69．20±27．58）U／L对比（102．43±47．29）U／L、（i58．00±39．15）U／L对比（229．50±105．20）U／L和（2．08±0．30）mmol／L对比（2．58±1．02）mmol／L，P值均〈0．05]；肝组织纤维化程度（s）显著改善（0．67±0．52对比2．50±0．40，P〈0．05）；TNFα、NF-κB及HMG-CoA还原酶的mRNA表达明显下调（P值均〈0．05），TNFα和NF-κB的蛋白质表达也明显下调（P值均〈0．05）。相对于姜黄素组，衍生物组大鼠肝指数及血清ALT、AST明显下降[分别为4．88％±0．62％对比5．16％±0．61％、（69．20±27．58）U／L对比（82．5±33．23）U／L和（158．00±39．15）U／L对比（211．75±106．30）U／L，P值均〈0．05】；肝组织脂肪变（F）及炎症（G）程度明显减轻（分别为1．17±0．41对比2．20±1．10和I．50±0．55对比2．40±0．58，P值均〈0．05）；TNFα、NF-κB和HMG-CoA还原酶的mRNA表达显著下调（P值均〈0．05）。结论相对于传统的姜黄素，水溶性姜黄素衍生物明显延缓实验性脂肪肝大鼠的纤维化进程，改善脂质代谢。

Objective To observe the effects of curcumin derivative on non-alcoholic steatohepatitis （NASH）. Methods 60 SD male rats were randomly divided into 5 groups. The NASH model was induced by high fat diet combined with carbon tetrachloride. These rats were then treated with curcumin and curcumin derivative, saline treating group as control. The serum biochemical parameters and liver histological examinations were observed. The TNF α, NF- KB and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR. The protein expressions of TNF α and NF- K B were detected by western blot. Results Compared with the saline group, A remarkable reduction was observed in serum ALT （U/L）, AST （U/L） and TC （mmol/L） in rats treated with curcumin derivatives [（69.20 ±27.58） vs （102.43 ± 47.29）,（158.00 ± 39.15） vs （229.50 ± 105.20） and （2.08±0.30） vs （2.58 ±1.02）, P 〈 0.05]. The degrees of fibro- sis were significantly alleviated; Compared with curcumin group, liver index and serum ALT, AST of curcumin derivative group were also significantly decreased [（4.88 ± 0.62）vs （5.16 ± 0.61）; （69.20 ±27.58） vs （82.5 ± 33.23）; （158.00 ± 39.15） vs （211.75 ± 106.30）, P 〈 0.05]; The liver steatosis and inflammation grade were also significantly improved .The gene transcriptions of TNα, NF- 1〈 B and HMG-CoA reduc- tase in curcumin derivative group were significantly lower than those in curcumin and saline group （P 〈 0.05）. Conclusion These results indicate that the water-soluble curcumin derivative displays superior bioavailability to the parent curcumin, which can effectively improve the lipid metabolism and delay the progression of hepatic fibrosis in rats with steatohepatitis.