姜黄素对酒精性肝损伤保护作用的实验研究
摘要
目的建立酒精性肝损伤大鼠模型,观察姜黄素对酒精性肝损伤大鼠肝脏氧化应激指标SOD,MDA和NO,血清ALT,AST和ALP水平及肝组织中NF-κB表达的影响,以探讨姜黄素是否能抑制脂质过氧化及NF-κB的过度表达,从而减轻或防治酒精诱导的肝损伤。
方法将40只SD大鼠随机分为对照组、模型组、姜黄素治疗Ⅰ组(40mg/kg)、姜黄素治疗Ⅱ组(80mg/kg)和姜黄素治疗Ⅲ组(160mg/kg),每组8只大鼠。除对照组用等量生理盐水灌胃外,其它组均采用56°白酒6.72g/(kg.d)每日灌胃一次的方法制作酒精性肝病大鼠模型,6周后姜黄素治疗Ⅰ、Ⅱ、Ⅲ组分别加用姜黄素40mg/kg、80mg/kg、160mg/kg灌胃。至12周末,处死大鼠,检测血清中ALT、AST及ALP水平及肝组织匀浆中SOD活性、MDA及NO含量,免疫组化法测定肝组织中NF-κB的表达,并常规HE染色观察肝脏病理变化。
结果与对照组相比,模型组大鼠血清ALT、AST及ALP水平显著升高(86.4±7.5vs 33.5±10.3,201.0±16.8 vs116.5±12.0,205.1±20.0 vs104.6±9.4,P＜0.01);肝组织SOD活性明显下降(80.21±4.55 vs180.24±27.53,P＜0.01),MDA及NO含量显著升高(3.29±0.34 vs1.35±0.12,4.37±0.21 vs 2.72±0.13,P＜0.01)。与模型组相比,各姜黄素治疗组血清ALT、AST及ALP水平明显降低(66.5±9.6/52.4±12.0/40.9±7.9 vs86.4±7.5,171.4±10.8/145.8±11.9/135.0±11.8 vs201.0±16.8.76.4±13.7/146.9±13.8/127.1±12.6 vs 205.1±20.0,P＜0.05 or P＜0.01);肝组织MDA及NO含量均显著降低(2.84±0.27/1.95±0.23/1.95±0.23 vs 3.29±0.34,4.01±0.17/3.60±0.16/3.60±0.16 vs4.37±0.21,P＜0.05 or P＜0.01),而SOD活性明显提高(92.36±6.47/117.69±21.96/146.70±27.36 vs 80.21±4.55,P＜0.05 0r P＜0.01),其中以Ⅱ、Ⅲ治疗组较为显著。免疫组化结果显示模型组大鼠肝组织中有NF-κB表达增强,而在各姜黄素治疗组大鼠肝组织中表达减弱。旺染色示模型组大鼠肝细胞出现不同程度的脂肪变性,伴有点、灶状坏死,炎性细胞浸润,各姜黄素治疗组肝脏病理变化不同程度的轻于模型组。
结论姜黄素能通过抑制酒精中毒大鼠脂质过氧化和肝组织中NF-κB的表达,从而减轻或防治酒精诱导的肝损伤。
Objective To reproduce an experimental model of alcoholic liver injury in rats and to investigate the effects of curcumin on lipid peroxidation and expression of nuclear factorκB induced by ethanol in rats.
Methods 40 Sprague-Dawley rats were randomly divided into five groups(8 rats/ group):control group,model group,curcumin treatment(40,80,160mg/kg) groups,control group intragastrically infused with normal saline,the other groups intragastrically infused with 56%(v/v)of ethanol,6.72g/(kg.d),after 6 weeks, curcumin treatment(40,80,160mg/kg)groups respectively added curcumin 40mg/kg,80mg/kg,160mg/kg.At the end of 12 weeks,all rats were killed.Levels of serum ALT,AST,ALP were measured.SOD,MDA,NO contents in the liver tissue were determined.The expression of NF-κB in the liver tissue were determined with immunohistochemical analysis and liver samples were obtained for routine histological examination.
Results The serum ALT,AST,ALP levels and the contents of MDA,NO in the liver tissue were significantly increased in model group than in control group (86.4±7.5 vs 33.5±10.3,201.0±16.8 vs 116.5±12.0,205.1±20.0 vs 104.6±9.4, 3.29±0.34 vs 1.35±0.12,4.37±0.21 vs 2.72±0.13,P＜0.01),SOD activity was markedly decreased(80.21±4.55 vs 180.24±27.53,P＜0.01).However,curcumin treatment groups markedly degraded the levels of serum ALT,AST,ALP,as well as the contents of MDA,NO in the liver tissue(66.5±9.6/52.4±12.0/40.9±7.9 vs86.4±7.5, 171.4±10.8/145.8±11.9/135.0±11.8 vs 201.0±16.8,76.4±13.7/146.9±13.8/127.1±12.6 vs 205.1±20.0,2.84±0.27/1.95±0.23/1.95±0.23 vs 3.29±0.34,4.01±0.17/3.60±0.16/ 3.60±20.16 vs 4.37±0.21,P＜0.05 or P＜0.01).Inversely,the SOD activity was elevated (92.36±6.47/117.69±21.96/146.70±27.36 vs 80.21±4.55,P＜0.05 or P＜0.01). Immunostaining for NF-κB showed that intensity of staining in model group was strong,degree of staining were decreased in groups treated with curcumin.Liver histological changes in model group showed obviously steatosis,focal necrosis and inflammatory cell infiltration,in curcumin treatment groups,the pathological changes were milder to varying degrees.
Conclusion Curcumin can relieve or prevent alcohol intoxication induced liver injury in rats by inhibiting lipid peroxidation and the expression of NF-κB.
方法将40只SD大鼠随机分为对照组、模型组、姜黄素治疗Ⅰ组(40mg/kg)、姜黄素治疗Ⅱ组(80mg/kg)和姜黄素治疗Ⅲ组(160mg/kg),每组8只大鼠。除对照组用等量生理盐水灌胃外,其它组均采用56°白酒6.72g/(kg.d)每日灌胃一次的方法制作酒精性肝病大鼠模型,6周后姜黄素治疗Ⅰ、Ⅱ、Ⅲ组分别加用姜黄素40mg/kg、80mg/kg、160mg/kg灌胃。至12周末,处死大鼠,检测血清中ALT、AST及ALP水平及肝组织匀浆中SOD活性、MDA及NO含量,免疫组化法测定肝组织中NF-κB的表达,并常规HE染色观察肝脏病理变化。
结果与对照组相比,模型组大鼠血清ALT、AST及ALP水平显著升高(86.4±7.5vs 33.5±10.3,201.0±16.8 vs116.5±12.0,205.1±20.0 vs104.6±9.4,P＜0.01);肝组织SOD活性明显下降(80.21±4.55 vs180.24±27.53,P＜0.01),MDA及NO含量显著升高(3.29±0.34 vs1.35±0.12,4.37±0.21 vs 2.72±0.13,P＜0.01)。与模型组相比,各姜黄素治疗组血清ALT、AST及ALP水平明显降低(66.5±9.6/52.4±12.0/40.9±7.9 vs86.4±7.5,171.4±10.8/145.8±11.9/135.0±11.8 vs201.0±16.8.76.4±13.7/146.9±13.8/127.1±12.6 vs 205.1±20.0,P＜0.05 or P＜0.01);肝组织MDA及NO含量均显著降低(2.84±0.27/1.95±0.23/1.95±0.23 vs 3.29±0.34,4.01±0.17/3.60±0.16/3.60±0.16 vs4.37±0.21,P＜0.05 or P＜0.01),而SOD活性明显提高(92.36±6.47/117.69±21.96/146.70±27.36 vs 80.21±4.55,P＜0.05 0r P＜0.01),其中以Ⅱ、Ⅲ治疗组较为显著。免疫组化结果显示模型组大鼠肝组织中有NF-κB表达增强,而在各姜黄素治疗组大鼠肝组织中表达减弱。旺染色示模型组大鼠肝细胞出现不同程度的脂肪变性,伴有点、灶状坏死,炎性细胞浸润,各姜黄素治疗组肝脏病理变化不同程度的轻于模型组。
结论姜黄素能通过抑制酒精中毒大鼠脂质过氧化和肝组织中NF-κB的表达,从而减轻或防治酒精诱导的肝损伤。
Objective To reproduce an experimental model of alcoholic liver injury in rats and to investigate the effects of curcumin on lipid peroxidation and expression of nuclear factorκB induced by ethanol in rats.
Methods 40 Sprague-Dawley rats were randomly divided into five groups(8 rats/ group):control group,model group,curcumin treatment(40,80,160mg/kg) groups,control group intragastrically infused with normal saline,the other groups intragastrically infused with 56%(v/v)of ethanol,6.72g/(kg.d),after 6 weeks, curcumin treatment(40,80,160mg/kg)groups respectively added curcumin 40mg/kg,80mg/kg,160mg/kg.At the end of 12 weeks,all rats were killed.Levels of serum ALT,AST,ALP were measured.SOD,MDA,NO contents in the liver tissue were determined.The expression of NF-κB in the liver tissue were determined with immunohistochemical analysis and liver samples were obtained for routine histological examination.
Results The serum ALT,AST,ALP levels and the contents of MDA,NO in the liver tissue were significantly increased in model group than in control group (86.4±7.5 vs 33.5±10.3,201.0±16.8 vs 116.5±12.0,205.1±20.0 vs 104.6±9.4, 3.29±0.34 vs 1.35±0.12,4.37±0.21 vs 2.72±0.13,P＜0.01),SOD activity was markedly decreased(80.21±4.55 vs 180.24±27.53,P＜0.01).However,curcumin treatment groups markedly degraded the levels of serum ALT,AST,ALP,as well as the contents of MDA,NO in the liver tissue(66.5±9.6/52.4±12.0/40.9±7.9 vs86.4±7.5, 171.4±10.8/145.8±11.9/135.0±11.8 vs 201.0±16.8,76.4±13.7/146.9±13.8/127.1±12.6 vs 205.1±20.0,2.84±0.27/1.95±0.23/1.95±0.23 vs 3.29±0.34,4.01±0.17/3.60±0.16/ 3.60±20.16 vs 4.37±0.21,P＜0.05 or P＜0.01).Inversely,the SOD activity was elevated (92.36±6.47/117.69±21.96/146.70±27.36 vs 80.21±4.55,P＜0.05 or P＜0.01). Immunostaining for NF-κB showed that intensity of staining in model group was strong,degree of staining were decreased in groups treated with curcumin.Liver histological changes in model group showed obviously steatosis,focal necrosis and inflammatory cell infiltration,in curcumin treatment groups,the pathological changes were milder to varying degrees.
Conclusion Curcumin can relieve or prevent alcohol intoxication induced liver injury in rats by inhibiting lipid peroxidation and the expression of NF-κB.
引文
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[13]Nanji AA,Jokelainen K,Lau GK,et al.Arginine reverses ethanol-induced inflammatory and fibrofic changes in liver despite continued ethanol administration.[J]Pharmacol Exp Ther.2001;299(3):832-9.
[14]Sailer R,Meier R,Brignoli R.The use of silymarin in the treatment of liver diseases.Drugs.[J]2001;61(14):2035-63.
[15]Nanji AA,Jokelainen K,Tipoe GL,et al.Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration.[J]Pharmacol Exp Ther.2001;299(2):638-44.
[16]Uesugi T,Froh M,Arteel GE,et al.Delivery of IkappaB superrepressor gene with adenovirus reduces early alcohol-induced liver injury in rats.[J]Hepatology.2001;34(6):1149-57.
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