CAJ | 학술논문

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50 mg/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(TNF α)、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,Western blot检测TNF α及NF-κB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-Wallis H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、(158.00±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);TNF α、NF-κB及HMG-CoA还原酶的mRNA表达明显下调(P值均<0.05),TNF α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1.50±0.55对比2.40±0.58,P值均<0.05);TNF α、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. 目的觀察薑黃素衍生物對實驗性非酒精性脂肪性肝炎(NASH)的治療作用.方法 60隻雄性SD大鼠隨機分為正常組、模型組、等滲鹽水對照組(等滲鹽水組)、薑黃素灌胃組(薑黃素組)、薑黃素衍生物靜脈註射組(衍生物組),每組12隻.通過高脂飼料結閤四氯化碳的複閤方式建立大鼠NASH模型.造模後分彆給予薑黃衍生物尾靜脈註射及薑黃素灌胃治療(劑量50 mg/kg),等滲鹽水作為對照.治療結束後取血及肝組織,計算肝指數,進行血脂和肝功能指標檢測及病理組織學檢查.RT-PCR法檢測肝組織中腫瘤壞死因子α(TNF α)、覈轉錄因子-κB(NF-κB)、羥甲戊二單酰輔酶A(HMG-CoA)還原酶的mRNA轉錄水平,Western blot檢測TNF α及NF-κB的蛋白質錶達水平.多組計量資料比較採用成組設計的方差分析、Kruskal-Wallis H檢驗,兩兩比較採用LSD法、成組設計的Wilcoxon秩和檢驗,P<0.05為差異有統計學意義.結果與等滲鹽水組比較,衍生物組大鼠血清ALT、AST和總膽固醇水平明顯下降[分彆為(69.20±27.58)U/L對比(102.43±47.29)U/L、(158.00±39.15)U/L對比(229.50±105.20)U/L和(2.08±0.30)mmol/L對比(2.58±1.02)mmol/L,P值均<0.05];肝組織纖維化程度(S)顯著改善(0.67±0.52對比2.50±0.40,P<0.05);TNF α、NF-κB及HMG-CoA還原酶的mRNA錶達明顯下調(P值均<0.05),TNF α和NF-κB的蛋白質錶達也明顯下調(P值均<0.05).相對于薑黃素組,衍生物組大鼠肝指數及血清ALT、AST明顯下降[分彆為4.88%±0.62%對比5.16%±0.61%、(69.20±27.58)U/L對比(82.5±33.23)U/L和(158.00±39.15)U/L對比(211.75±106.30)U/L,P值均<0.05];肝組織脂肪變(F)及炎癥(G)程度明顯減輕(分彆為1.17±0.41對比2.20±1.10和1.50±0.55對比2.40±0.58,P值均<0.05);TNF α、NF-κB和HMG-CoA還原酶的mRNA錶達顯著下調(P值均<0.05).結論相對于傳統的薑黃素,水溶性薑黃素衍生物明顯延緩實驗性脂肪肝大鼠的纖維化進程,改善脂質代謝.
목적 관찰강황소연생물대실험성비주정성지방성간염(NASH)적치료작용.방법 60지웅성SD대서수궤분위정상조、모형조、등삼염수대조조(등삼염수조)、강황소관위조(강황소조)、강황소연생물정맥주사조(연생물조),매조12지.통과고지사료결합사록화탄적복합방식건립대서NASH모형.조모후분별급여강황연생물미정맥주사급강황소관위치료(제량50 mg/kg),등삼염수작위대조.치료결속후취혈급간조직,계산간지수,진행혈지화간공능지표검측급병리조직학검사.RT-PCR법검측간조직중종류배사인자α(TNF α)、핵전록인자-κB(NF-κB)、간갑무이단선보매A(HMG-CoA)환원매적mRNA전록수평,Western blot검측TNF α급NF-κB적단백질표체수평.다조계량자료비교채용성조설계적방차분석、Kruskal-Wallis H검험,량량비교채용LSD법、성조설계적Wilcoxon질화검험,P<0.05위차이유통계학의의.결과 여등삼염수조비교,연생물조대서혈청ALT、AST화총담고순수평명현하강[분별위(69.20±27.58)U/L대비(102.43±47.29)U/L、(158.00±39.15)U/L대비(229.50±105.20)U/L화(2.08±0.30)mmol/L대비(2.58±1.02)mmol/L,P치균<0.05];간조직섬유화정도(S)현저개선(0.67±0.52대비2.50±0.40,P<0.05);TNF α、NF-κB급HMG-CoA환원매적mRNA표체명현하조(P치균<0.05),TNF α화NF-κB적단백질표체야명현하조(P치균<0.05).상대우강황소조,연생물조대서간지수급혈청ALT、AST명현하강[분별위4.88%±0.62%대비5.16%±0.61%、(69.20±27.58)U/L대비(82.5±33.23)U/L화(158.00±39.15)U/L대비(211.75±106.30)U/L,P치균<0.05];간조직지방변(F)급염증(G)정도명현감경(분별위1.17±0.41대비2.20±1.10화1.50±0.55대비2.40±0.58,P치균<0.05);TNF α、NF-κB화HMG-CoA환원매적mRNA표체현저하조(P치균<0.05).결론상대우전통적강황소,수용성강황소연생물명현연완실험성지방간대서적섬유화진정,개선지질대사.
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 indced 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-κB and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR.The protein expressions of TNF αand NF-κB 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 derivatiYeS[(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 fibrosis 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 TNF α,NF- κB and HMG-CoA reductase 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.