CAJ | 학술논문

目的：研究胰岛素抵抗（IR）的慢性丙型肝炎（CHC）患者外周血及肝组织内源性大麻素系统的变化。方法采用高效液相色谱-质谱联用技术检测CHC患者和CHC合并IR患者外周血内源性大麻素花生四烯酸乙醇胺（AEA）和花生四烯酰甘油（2-AG）水平，应用 RT-PCR及 Western印迹检测肝组织大麻素受体1（CB1R）及脂肪酸酰胺水解酶（FAAH）的表达，数据行 t检验。结果与CHC患者相比，CHC合并IR患者外周血AEA水平升高[（6．80±1．70）pmol/mL比（3．88±0．63）pmol/mL ，t＝8．053，P＜0．01]；肝组织CB1R mRNA水平（1．7±0．4比1．0±0．2，t＝4．696，P＜0．01）和CB1R蛋白水平（0．8±0．2比0．4±0．1，t＝5．367，P＜0．01）增加；FAAH mRNA 水平（0．5±0．1比1．0±0．3，t＝4．743，P＜0．01）和FAAH蛋白水平（0．5±0．1比0．8±0．3，t＝2．846，P＜0．01）下降。与胰岛素抵抗指数（HOMA-IR）＜4的患者相比，HOMA-IR指数≥4的患者AEA水平升高[（7．53±1．85） pmol/mL比（5．56±1．40） pmol/mL （t＝2．986， P＜0．05）]；肝组织CB1 mRNA水平（2．3±0．65比1．4±0．35，t＝2．986，P＜0．05）和CB1R蛋白水平（1．2±0．3比0．9±0．2，t＝2．038，P＜0．05）升高，FAAH mRNA 水平（0．3±0．08比0．6±0．15，t＝4．076，P＜0．01）和 FAAH 蛋白水平（0．2±0．05比0．4±0．1，t＝3．464，P＜0．05）下降。结论随着IR程度加重，CHC患者外周血AEA水平升高；肝组织CB1R表达增加而FAAH表达减少。
목적：연구이도소저항（IR）적만성병형간염（CHC）환자외주혈급간조직내원성대마소계통적변화。방법채용고효액상색보-질보련용기술검측CHC환자화CHC합병IR환자외주혈내원성대마소화생사희산을순알（AEA）화화생사희선감유（2-AG）수평，응용 RT-PCR급 Western인적검측간조직대마소수체1（CB1R）급지방산선알수해매（FAAH）적표체，수거행 t검험。결과여CHC환자상비，CHC합병IR환자외주혈AEA수평승고[（6．80±1．70）pmol/mL비（3．88±0．63）pmol/mL ，t＝8．053，P＜0．01]；간조직CB1R mRNA수평（1．7±0．4비1．0±0．2，t＝4．696，P＜0．01）화CB1R단백수평（0．8±0．2비0．4±0．1，t＝5．367，P＜0．01）증가；FAAH mRNA 수평（0．5±0．1비1．0±0．3，t＝4．743，P＜0．01）화FAAH단백수평（0．5±0．1비0．8±0．3，t＝2．846，P＜0．01）하강。여이도소저항지수（HOMA-IR）＜4적환자상비，HOMA-IR지수≥4적환자AEA수평승고[（7．53±1．85） pmol/mL비（5．56±1．40） pmol/mL （t＝2．986， P＜0．05）]；간조직CB1 mRNA수평（2．3±0．65비1．4±0．35，t＝2．986，P＜0．05）화CB1R단백수평（1．2±0．3비0．9±0．2，t＝2．038，P＜0．05）승고，FAAH mRNA 수평（0．3±0．08비0．6±0．15，t＝4．076，P＜0．01）화 FAAH 단백수평（0．2±0．05비0．4±0．1，t＝3．464，P＜0．05）하강。결론수착IR정도가중，CHC환자외주혈AEA수평승고；간조직CB1R표체증가이FAAH표체감소。
Objective To study the change of endocannabinoid system in the peripheral circulation and liver in patients with chronic hepatitis C (CHC) and insulin resistance (IR) .Methods Circulating endocannabinoid (anandamide and 2-AG) levels were determined by liquid chromatography/mass spectrometry . The expression levels of cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) in liver was detected by RT-PCR and western blot .The data was checked by t test .Results Compared to patients with CHC ,in the patients with CHC and IR had increased ,the anandamide level was significantly increased in the peripheral circulation [(6 .80 ± 1 .70) vs (3 .88 ± 0 .63) pmol/ml ,t=8 .053 ,P<0 .01] in patients with CHC and IR ,CB1R mRNA (1 .7 ± 0 .4 vs 1 .0 ± 0 .2 ,t=4 .696 ,P<0 .01) and protein levels (0 .8 ± 0 .2 vs 0 .4 ± 0 .1 ,t=5 .367 ,P<0 .01) in liver were significantly increased in patients with CHC and IR ,and FAAH mRNA level (0 .5 ± 0 .1 vs 1 .0 ± 0 .3 ,t=4 .743 ,P<0 .01) and protein levels (0 .5 ± 0 .1 vs 0 .8 ± 0 .3 ,t=2 .846 , P< 0 .01) were significantly decreased in patients with CHC and IR .Compared to patients with homeostasis model assessment of insulin resistance (HOMA-IR) < 4 ,in patients with HOMA-IR≥ 4 ,had increased the anandamide level increased[(7.53±1.85)vs(5.56±1.40)pmol/ml,t= 2.986,P< 0.05)]wassignificantlyincreasedinpatientswith HOMA-IR≥4 ,CB1R mRNA level (2 .3 ± 0 .65 vs 1 .4 ± 0 .35 ,t=2 .986 ,P<0 .05) and protein levels (1 .2 ± 0 .3 vs 0 .9 ±0 .2 ,t=2 .038 ,P<0 .05) was significantly decreased in patients with HOMA-IR≥4 ,FAAH mRNA level (0 .3 ± 0 .08 vs 0 .6 ± 0 .15 ,t=4 .076 , P< 0 .01) and protein levels (0 .2 ± 0 .05 vs 0 .4 ± 0 .1 , t= 3 .464 , P< 0 .05) was significantly decreased in patients with HOMA-IR≥4 .Conclusion In patients with CHC and the development of IR ,the anandamide and CB1R levels were increasesd ,but level of FAAH was decreasesd in liver .