中华预防医学杂志
中華預防醫學雜誌
중화예방의학잡지
CHINESE JOURNAL OF
2010年
1期
24-29
,共6页
韩知峡%杨澜%张亮%许川%舒为群
韓知峽%楊瀾%張亮%許川%舒為群
한지협%양란%장량%허천%서위군
儿茶素%微囊藻属%细胞色素P450 CYP2E1%肝细胞%基因表达
兒茶素%微囊藻屬%細胞色素P450 CYP2E1%肝細胞%基因錶達
인다소%미낭조속%세포색소P450 CYP2E1%간세포%기인표체
Catechin%Microcystis%Cytochrome P-450 CYP2E1%Hepatocytes%Gene expression
目的 探讨表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)对微囊藻毒素LR(microcystin-LR,MC-LR)诱导小鼠肝细胞氧化损伤的化学拮抗作用及细胞色素P450 2E1(eytochrome P450 2E1,CYP2E1)表达的影响.方法 24只无特定病原体(specific pathogen free,SPF)级雄性BALB/c小鼠数字表法随机分为对照组、MC-LR染毒组、EGCG低剂量拮抗组、EGCG高剂量拮抗组,每组6只,持续暴露14 d.第15天处死小鼠,对肝脏脏体比、病理改变、抗氧化酶及脂质过氧化物水平、CYP2E1基因和蛋白表达进行检测和分析.结果 (1)EGCG可拮抗MC-LR所致小鼠体重下降,减轻MC-LR造成的肝脏病理损伤.(2)MC-LR染毒组小鼠脂质过氧化物丙二醛(malonaldehyde,MDA)水平[(2.87±0.03)nmol/mg prot]、超氧化物歧化酶(superoxide dismutase,SOD)水平[(168.18±2.86)U/mg prot]与EGCG两处理组相比,差异均有统计学意义[低、高剂量组MDA值分别为(2.37±0.05)、(1.44±0.05)nmol/mg prot,F=906.63,P<0.01;SOD值分别为(176.55±2.98)、(184.89±1.53)U/mg prot,F=32.32,P<0.01].(3)MC-LR可显著上调CYP2E1mRNA和蛋白表达平均吸光度值(CYP2E1 mRNA表达水平:MC-LR染毒组为1.41±0.26,对照组为0.86±0.13,t=-4.22,P=0.003;蛋白表达水平:MC-LR染毒组为0.24±0.03,对照组为0.12±0.02,t=-9.21,P<0.05),EGCG可显著降低该表达(低、高剂量组CYP2E1 mRNA表达水平分别为1.09±0.08、0.99±0.09,与MC-LR染毒组比较,F=9.03,P=0.004;蛋白表达水平分别为0.21 ±0.03、0.14±0.02,与MC-LR染毒组比较,F=24.76,P<0.05).结论 EGCG可抑制MC-LR诱导CYP2E1的表达,对MC-LR诱导的肝细胞氧化损伤有一定拮抗作用.
目的 探討錶沒食子兒茶素沒食子痠酯(epigallocatechin-3-gallate,EGCG)對微囊藻毒素LR(microcystin-LR,MC-LR)誘導小鼠肝細胞氧化損傷的化學拮抗作用及細胞色素P450 2E1(eytochrome P450 2E1,CYP2E1)錶達的影響.方法 24隻無特定病原體(specific pathogen free,SPF)級雄性BALB/c小鼠數字錶法隨機分為對照組、MC-LR染毒組、EGCG低劑量拮抗組、EGCG高劑量拮抗組,每組6隻,持續暴露14 d.第15天處死小鼠,對肝髒髒體比、病理改變、抗氧化酶及脂質過氧化物水平、CYP2E1基因和蛋白錶達進行檢測和分析.結果 (1)EGCG可拮抗MC-LR所緻小鼠體重下降,減輕MC-LR造成的肝髒病理損傷.(2)MC-LR染毒組小鼠脂質過氧化物丙二醛(malonaldehyde,MDA)水平[(2.87±0.03)nmol/mg prot]、超氧化物歧化酶(superoxide dismutase,SOD)水平[(168.18±2.86)U/mg prot]與EGCG兩處理組相比,差異均有統計學意義[低、高劑量組MDA值分彆為(2.37±0.05)、(1.44±0.05)nmol/mg prot,F=906.63,P<0.01;SOD值分彆為(176.55±2.98)、(184.89±1.53)U/mg prot,F=32.32,P<0.01].(3)MC-LR可顯著上調CYP2E1mRNA和蛋白錶達平均吸光度值(CYP2E1 mRNA錶達水平:MC-LR染毒組為1.41±0.26,對照組為0.86±0.13,t=-4.22,P=0.003;蛋白錶達水平:MC-LR染毒組為0.24±0.03,對照組為0.12±0.02,t=-9.21,P<0.05),EGCG可顯著降低該錶達(低、高劑量組CYP2E1 mRNA錶達水平分彆為1.09±0.08、0.99±0.09,與MC-LR染毒組比較,F=9.03,P=0.004;蛋白錶達水平分彆為0.21 ±0.03、0.14±0.02,與MC-LR染毒組比較,F=24.76,P<0.05).結論 EGCG可抑製MC-LR誘導CYP2E1的錶達,對MC-LR誘導的肝細胞氧化損傷有一定拮抗作用.
목적 탐토표몰식자인다소몰식자산지(epigallocatechin-3-gallate,EGCG)대미낭조독소LR(microcystin-LR,MC-LR)유도소서간세포양화손상적화학길항작용급세포색소P450 2E1(eytochrome P450 2E1,CYP2E1)표체적영향.방법 24지무특정병원체(specific pathogen free,SPF)급웅성BALB/c소서수자표법수궤분위대조조、MC-LR염독조、EGCG저제량길항조、EGCG고제량길항조,매조6지,지속폭로14 d.제15천처사소서,대간장장체비、병리개변、항양화매급지질과양화물수평、CYP2E1기인화단백표체진행검측화분석.결과 (1)EGCG가길항MC-LR소치소서체중하강,감경MC-LR조성적간장병리손상.(2)MC-LR염독조소서지질과양화물병이철(malonaldehyde,MDA)수평[(2.87±0.03)nmol/mg prot]、초양화물기화매(superoxide dismutase,SOD)수평[(168.18±2.86)U/mg prot]여EGCG량처리조상비,차이균유통계학의의[저、고제량조MDA치분별위(2.37±0.05)、(1.44±0.05)nmol/mg prot,F=906.63,P<0.01;SOD치분별위(176.55±2.98)、(184.89±1.53)U/mg prot,F=32.32,P<0.01].(3)MC-LR가현저상조CYP2E1mRNA화단백표체평균흡광도치(CYP2E1 mRNA표체수평:MC-LR염독조위1.41±0.26,대조조위0.86±0.13,t=-4.22,P=0.003;단백표체수평:MC-LR염독조위0.24±0.03,대조조위0.12±0.02,t=-9.21,P<0.05),EGCG가현저강저해표체(저、고제량조CYP2E1 mRNA표체수평분별위1.09±0.08、0.99±0.09,여MC-LR염독조비교,F=9.03,P=0.004;단백표체수평분별위0.21 ±0.03、0.14±0.02,여MC-LR염독조비교,F=24.76,P<0.05).결론 EGCG가억제MC-LR유도CYP2E1적표체,대MC-LR유도적간세포양화손상유일정길항작용.
Objective To evaluate the effects of antagonistic action of epigallocatechin-3-gallate(EGCG) on microcystin LR (MC-LR) induced oxidative damage on mice and the expression of cytochrome P450 2E1 ( CYP2E1 ) which was one of phase Ⅰ detoxification enzymes. MethodsA total of 24 specific pathogen free(SPF) male BALB/c mice were randomly divided into four groups,including control group,MC-LR group,low concentration EGCG group, and high concentration EGCG group. Mice were sacrificed on the 15th day, body weight, and the relative organ weight, liver antioxidant enzyme level and lipid peroxidation product, liver histopathology and CYP2E1 gene and protein expression were detected and analyzed respectively. Results( 1 ) EGCG could antagonise the liver injury which had been damaged by MC-LR.(2) The malonaldehyde (MDA) level ( (2. 87 ±0. 03 ) nmol/mg prot)and superoxide dismutase(SOD) level((168. 18±+2. 86) U/mg prot)in MC-LR group were significantly different when compared with the two EGGG treatment groups ( the MDA values of the low and high concentration EGCG group were (2. 37±0. 05) nmol/mg prot and ( 1.44±0. 05 ) nmol/mg prot, F = 906. 63, P < 0. 01 ; the SOD values were(176.55+2.98) U/mg prot and (184.89±1.53) U/mg prot, F=32.32,P<0.01). (3) MC-LR up-regulated the mRNA and protein expression of CYP2E1 ( the mRNA values of MC-LR group and control were 1.41±0. 26,0. 86±0. 13, t = - 4. 22, P = 0. 003 ; the protein values of MC-LR group and control were 0. 24±0. 03,0. 12±0. 02 ,t = - 9. 21 ,P < 0. 05 ). EGCG down-regulated the mRNA ( the values of the low and high concentration EC, CG group were 1.09±0. 08,0. 99±0. 09, F = 9. 03, P = 0. 004 ) and protein expression (the values of the low and high concentration EGCG group were 0. 21±0. 03,0. 14±0. 02,F =24. 76 ,P < 0. 05 )of CYP2E1 which activated by MC-LR. ConclusionThe up-regulation of CYP2E1 which induced by MC-LR was inhibited by EGCG intervention. EGCG might antagonize the oxidation damage of hepatocytes in a certain degree.
