乙型肝炎病毒对肝脂肪变患者肝细胞固醇调节元件结合蛋白表达的影响
을형간염병독대간지방변환자간세포고순조절원건결합단백표체적영향
Effect of HBV on the expression of SREBP in the hepatocyte of chronic hepatitis B patients combined with hepatic fatty change
  • 万方数据
    中华肝脏病杂志 중화간장병잡지
    CHINESE JOURNAL OF HEPATOLOGY
    2011年 8期 608-613 ,共6页

    江萃英%曾维琼%陈压西%戴福宏%姜平

    강췌영%증유경%진압서%대복굉%강평

    乙型肝炎病毒%肝脂肪变%固醇调节元件结合蛋白 乙型肝炎病毒%肝脂肪變%固醇調節元件結閤蛋白
    을형간염병독%간지방변%고순조절원건결합단백
    Hepatitis B virus%Hepatic steatosis%Sterol regulatory element binding protein
    目的 探讨HBV对肝脂肪变患者肝细胞固醇调节元件结合蛋白(SREBPs)表达的影响.方法 收集我院感染科诊断为CHB合并肝脂肪变的患者55例,根据患者外周血清HBV DNA载量的不同分为3组:A组:HBV DNA≤103拷贝/ml的患者(15例);B组:103拷贝/ml＜HBV DNA＜105拷贝/ml的患者(18例); C组:HBV DNA≥105拷贝/ml的患者(22例).将C组抗病毒治疗后HBV DNA≤103拷贝/ml的10例患者分为C1组(治疗前)和C2组(治疗后);将C组抗病毒治疗后HBV DNA≥105拷贝/ml的12例患者分为C3组(治疗前)和C4组(治疗后).用油红O染色观察肝组织脂滴的变化;实时荧光定量PCR检测SREBP-1c及SREBP-2 mRNA的表达;免疫组织化学法检测SREBP-1c及SREBP-2蛋白的表达.多组间比较用单因素方差分析及q检验,配对样本t检验进行抗病毒前后两组间数据的比较.结果 (1)A、B、C组脂滴表 达的红色积分吸光度值分别为1004.27±218.63、1937.01±401.47、4133.79±389.28,各组间油红O红染程度不同(F=385.69,P＜0.01);C1、C2、C3、C4组脂滴表达的红色积分吸光度值分别为4020.84±326.64、1012.02±244.89、4189.18±329.21、4121.76±304.09,与C1组比较,C2组油红O红染程度下调,t=22.55,P＜0.01,差异有统计学意义;C4组与C3组比较,差异无统计学意义.(2)与A组比较,B组与C组SREBP-1c mRNA分别上调(1.218±0.130)倍、(1.798±0.118)倍,A、B、C组SREBP-1c mRNA表达水平比较,F=297.47,P＜0.01,差异有统计学意义.与A组比较,B组与C组SREBP-2 mRNA分别下调95.6%±11.8%、97.2%±15.3%,A、B、C组间SREBP-2 mRNA表达水平比较,差异无统计学意义.与C1组比较,C2组SREBP-1c mRNA表达水平下调71.4%±8.1%,t=11.224,P＜0.01,差异有统计学意义;与C1组比较,C2组SREBP-2 mRNA表达水平上调(1.034±0.155)倍,差异无统计学意义.与C3组比较,C4组SREBP-1c mRNA表达水平上调(1.012±0.206)倍,差异无统计学意义;与C3组比较,C4组SREBP-2 mRNA表达水平下调99.8%±18.3%,差异无统计学意义.(3)A、B、C组SREBP-1c蛋白表达量分别为36257.21±5709.79、50413.47±4989.28、71025.83±6047.13,3组SREBP-1c蛋白比较,F=178.26,P＜0.01,差异有统计学意义;A、B、C组SREBP-2蛋白表达量分别为32913.52±3951.21、32625.91±4025.06、34173.44±5316.25,3组比较,差异无统计学意义.C1、C2、C3、C4组SREBP-1c蛋白表达量分别为69832.16±4941.36、48735.47±5471.41、70871.69±5083.14、68913.32±5343.22,C1组与C2组比较,t=10.260,P＜0.01,差异有统计学意义;C3与C4组比较,差异无统计学意义.C1、C2、C3、C4组SREBP-2蛋白表达量分别为33980.21±4081.80、34011.50±3859.27、33610.12±4761.10、32915.66±5023.61,C1组与C2组比较,差异无统计学意义,C3组与C4组比较,差异无统计学意义.结论 HBV DNA可能通过干扰SREBP-1c的表达而参与了肝细胞脂肪变性的形成.
    목적 탐토HBV대간지방변환자간세포고순조절원건결합단백(SREBPs)표체적영향.방법 수집아원감염과진단위CHB합병간지방변적환자55례,근거환자외주혈청HBV DNA재량적불동분위3조:A조:HBV DNA≤103고패/ml적환자(15례);B조:103고패/ml＜HBV DNA＜105고패/ml적환자(18례); C조:HBV DNA≥105고패/ml적환자(22례).장C조항병독치료후HBV DNA≤103고패/ml적10례환자분위C1조(치료전)화C2조(치료후);장C조항병독치료후HBV DNA≥105고패/ml적12례환자분위C3조(치료전)화C4조(치료후).용유홍O염색관찰간조직지적적변화;실시형광정량PCR검측SREBP-1c급SREBP-2 mRNA적표체;면역조직화학법검측SREBP-1c급SREBP-2단백적표체.다조간비교용단인소방차분석급q검험,배대양본t검험진행항병독전후량조간수거적비교.결과 (1)A、B、C조지적표 체적홍색적분흡광도치분별위1004.27±218.63、1937.01±401.47、4133.79±389.28,각조간유홍O홍염정도불동(F=385.69,P＜0.01);C1、C2、C3、C4조지적표체적홍색적분흡광도치분별위4020.84±326.64、1012.02±244.89、4189.18±329.21、4121.76±304.09,여C1조비교,C2조유홍O홍염정도하조,t=22.55,P＜0.01,차이유통계학의의;C4조여C3조비교,차이무통계학의의.(2)여A조비교,B조여C조SREBP-1c mRNA분별상조(1.218±0.130)배、(1.798±0.118)배,A、B、C조SREBP-1c mRNA표체수평비교,F=297.47,P＜0.01,차이유통계학의의.여A조비교,B조여C조SREBP-2 mRNA분별하조95.6%±11.8%、97.2%±15.3%,A、B、C조간SREBP-2 mRNA표체수평비교,차이무통계학의의.여C1조비교,C2조SREBP-1c mRNA표체수평하조71.4%±8.1%,t=11.224,P＜0.01,차이유통계학의의;여C1조비교,C2조SREBP-2 mRNA표체수평상조(1.034±0.155)배,차이무통계학의의.여C3조비교,C4조SREBP-1c mRNA표체수평상조(1.012±0.206)배,차이무통계학의의;여C3조비교,C4조SREBP-2 mRNA표체수평하조99.8%±18.3%,차이무통계학의의.(3)A、B、C조SREBP-1c단백표체량분별위36257.21±5709.79、50413.47±4989.28、71025.83±6047.13,3조SREBP-1c단백비교,F=178.26,P＜0.01,차이유통계학의의;A、B、C조SREBP-2단백표체량분별위32913.52±3951.21、32625.91±4025.06、34173.44±5316.25,3조비교,차이무통계학의의.C1、C2、C3、C4조SREBP-1c단백표체량분별위69832.16±4941.36、48735.47±5471.41、70871.69±5083.14、68913.32±5343.22,C1조여C2조비교,t=10.260,P＜0.01,차이유통계학의의;C3여C4조비교,차이무통계학의의.C1、C2、C3、C4조SREBP-2단백표체량분별위33980.21±4081.80、34011.50±3859.27、33610.12±4761.10、32915.66±5023.61,C1조여C2조비교,차이무통계학의의,C3조여C4조비교,차이무통계학의의.결론 HBV DNA가능통과간우SREBP-1c적표체이삼여료간세포지방변성적형성.
    Objective To investigate the effect of HBV on the expression of Sterol regulatory element binding proteins( SREBP ) in the hepatocyte of patients with chronic hepatitis B(CHB) combined with hepatic fatty change. Methods 55 cases diagnosed as CHB combined with hepatic fatty change in our department were selected and liver biopsies were carried out. The patients were dividied into 3 groups, group A: HBV DNA ≤ 103copies/ml(15 cases), group B:103copies/ml ＜ HBV DNA ＜ 105copies/ml (18 cases)and group C:HBV DNA ≥ 105 copies/ml (22 cases). 10 patients with HBV DNA ≤ 103 copies/ml after antiviral therapy with Nucleoside analogues were seen as group C1 (before treatment)and group C2 (after treatment) respectively; 12 patients with HBV DNA ≥ 105 copies/ml after antiviral therapy were classified as group C3 (before treatment) and group C4 (after treatment). Lipid droplets in the hepatic tissue were observed with oil red staining. Real time PCR were performed to detect the expressions of SREBP-1c and SREBP-2 mRNA in the liver. The protein expressions of SREBP-1c and SREBP-2 were detected with immunohistochemistry staining. Statistic data were analysed with SPSS11.5 software. Results ( 1 ) Red integrated optical densities (IOD) reflected by lipid drops in group A, B and C are 1004.27±218.63, 1937.01 ±401.47 and 4133.79±389.28 respectively, the degree of oil red O in each group was different (F = 385.69, P ＜ 0.01 ) , which is increased as HBV DNA load increasing;Red IOD in group C1、 C2 and C3、 C4 are 4020.84 ± 326.64, 1012.02 ± 244.89, 4189.18 ± 329.21 and 4121.76 ± 304.09 respectively. Compared with group C1, the degree ofoil red O in group C2 is decreased and the difference is statistically significant( t = 22.55, P ＜ 0.01); However, the difference of the degree of oil red O between group C4 and C3 is not statistically significant. (2) Compared with group A, the expressions of SREBP-1c mRNA in group B and C are raised by 1.218±0.130 and 1.798±0.118 times respectively, among group A、 B、 C, the expressions of SREBP-1c mRNA are statistically significant different( F = 297.47, P＜0.01). The expressions of SREBP-2 mRNA in group B and C are decreased by 0.956 ± 0.118 and 0.972 ± 0.153 times as compared to group A. However, the difference of SREBP-2 mRNA expression among the 3 groups is not statistically significant( F = 0.568, P ＞ 0.05). Compared with group C1, SREBP-1c mRNA in group C2 is decreased by 0.714 ± 0.081 folds ( t = 11.224, P ＜ 0.01), while SREBP-2 mRNA in group C2 is raised by 1.034 ± 0.155 times( t = 0.692, P ＞ 0.05). SREBP- 1 c mRNA and SREBP-2 mRNA in group C4 are raised by 1.012±0.206 times and decreased by 0.998±0.183 times as compared to group C3 without difference found ( t = 0.196 or 0.031, P ＞ 0.05). (3) the expressions of SREBP-lc protein in group A、 B and C are 36 257.21 ± 5709.79,50413.47 ± 4989.28 and 71 025.83 ± 6047.13 respectively, and the difference is statistically significant among the 3 groups(F = 178.26, P ＜ 0.01); the expressions of SREBP-2 protein in group A、 B and C are 32 913.52 ± 3951.21, 32 625.91 ± 4025.06 and 34 173.44 ± 5316.25 respectively, but the difference is not statistically significant among the 3 groups( F = 0.562, P ＞ 0.05), SREBP-1c protein levels in group C1,C2, C3, C4 are 69832.16 ± 4941.36, 48735.47 ± 5471.41, 70871.69 ± 5083.14 and 68913.32 ± 5343.22 respectively, the difference of SREBP-1c protein levels between group C1 and C2 is statistically significant (t = 10.260, P ＜ 0.01); while the difference between group C3 and group C4 is not statistically significant( t = 1.558, P ＞ 0.05). The expressions of SREBP-2 protein in group C1, C2, C3 and C4 are 33 980.21 ± 4081.80,34011.50 ± 3859.27, 33610.12 ± 4761.10 and 32915.66 ± 5023.61 respectively, the difference of SREBP-2 protein levels in group C1 and group C2 is not statistically significant ( t = 0.038, P＞ 0.05) and same result exists between group C3 and group C4 ( t = 0.459, P ＞ 0.05). Conclusion HBV DNA may participate in the hepatic steatosis formation through interfering with the SREBP-1c expression.
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