摘要
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：HBVDNA≤10^3拷贝／ml的患者（15例）；B组：10^3拷贝／ml〈HBV DNA〈10^5拷贝／ml的患者（18例）；C组：HBVDNA≥10^5拷贝／ml的患者（22例）。将C组抗病毒治疗后HBV DNA≤10^3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≥10^5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口检验，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，JP〈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-2mRNA表达水平比较，差异无统计学意义。与C1组比较，C2组SREBP—1cmRNA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-2mRNA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-1cmRNA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-2mRNA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HBVDNA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。
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 〉 105copies/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-1 c and SREBP-2 were detected with immunohistochemistry staining. Statistic data were analysed with SPSS 11.5 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-1c protein in groupA, B and C are 36257.21 ±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 C 1 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-1 c expression.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2011年第8期608-613,共6页
Chinese Journal of Hepatology
基金
重庆市教委科学技术研究项目（KJ090310）
关键词
乙型肝炎病毒
肝脂肪变
固醇调节元件结合蛋白
Hepatitis B virus
Hepatic steatosis
Sterol regulatory element binding protein
