CAJ | 학술논문

目的探讨蛋白酶体抑制剂bortezomib对胆道梗阻大鼠肝脏的保护作用.方法将30只大鼠随机分为假手术组(SO组)、胆道梗阻对照组(Con组)和bortezomib实验组(Bor组).Con组通过胆总管结扎建立大鼠胆道梗阻模型,Bor组同法结扎胆总管并于术前1 d、术后第3天腹腔注射bortezomib,假手术组仅行剖腹和胆总管游离.所有大鼠均于术后7 d处死,处死前采集血清测定血清丙氨酸转氨酶(ALT),总胆红素(TB)和总胆汁酸(TBA)水平.免疫组化染色测定肝组织NF-κBp65含量.逆转录-聚合酶联反应测定肝脏组织中TNF-α mRNA水平.结果Con组与Bor组的TB和TBA水平并差异无统计学意义(P＞0.05),而Bor组的ALT水平[(92.4±21.4)μmo1/L]明显低于Con组[(145.7±33.5)μmol/L],P＜0.05.Bor组的NF-κB p65亚基阳性染色率(11.6%±2.7%)明显低于Con组(15.5%±4.3%),P＜0.05.而逆转录-聚合酶联反应发现,Bor组TNF-αmRNA相对表达量(1.0±0.2)明显低于Con组(1.3±0.4),P＜0.05.结论bortezomib可以通过抑制NF-κB的活化减少炎症反应的发生,从而减轻因胆道梗阻引起的肝脏损害.
목적탐토단백매체억제제bortezomib대담도경조대서간장적보호작용.방법장30지대서수궤분위가수술조(SO조)、담도경조대조조(Con조)화bortezomib실험조(Bor조).Con조통과담총관결찰건립대서담도경조모형,Bor조동법결찰담총관병우술전1 d、술후제3천복강주사bortezomib,가수술조부행부복화담총관유리.소유대서균우술후7 d처사,처사전채집혈청측정혈청병안산전안매(ALT),총담홍소(TB)화총담즙산(TBA)수평.면역조화염색측정간조직NF-κBp65함량.역전록-취합매련반응측정간장조직중TNF-α mRNA수평.결과Con조여Bor조적TB화TBA수평병차이무통계학의의(P＞0.05),이Bor조적ALT수평[(92.4±21.4)μmo1/L]명현저우Con조[(145.7±33.5)μmol/L],P＜0.05.Bor조적NF-κB p65아기양성염색솔(11.6%±2.7%)명현저우Con조(15.5%±4.3%),P＜0.05.이역전록-취합매련반응발현,Bor조TNF-αmRNA상대표체량(1.0±0.2)명현저우Con조(1.3±0.4),P＜0.05.결론bortezomib가이통과억제NF-κB적활화감소염증반응적발생,종이감경인담도경조인기적간장손해.
Objective To assess the protective effect of the proteasome inhibitor bortezomib on rat liver subjected to bile duct obstruction. Methods Thirty rats were divided randomly into three groups, which were sham-operation group (SO group), bile duct ligation control group (Con group) and bortezomib group (Bor group). All rats in the Con group underwent ligation of the common bile duct, and rats in the Bor group were given bortezomib intrabominally at-1 d, 4 d post-ligation of the common bile duct. All the rats were sacrificed at 7 d post-surgery. ALT, TB and TBA levels were determined. The expression of NF-κB p65 was assessed using immunohistological staining. RT-PCR was employed to detect TNF-α mRNA levels in liver samples. Results There was no significance in the levels of TB and TBA between Con and Bor groups. The ALT revel in the Bor group [(92.4±21.4)μmol/L]was significantly lower than that in the Con group [(145.7 ±33.5) μmol/L], P＜0.05. The positive staining rate of NF-κB p65 subunit in the Bor group showed significant lower value (11.6% ±2.7 % ) compared to that in the Con group (15.5 %±4.3 % ), P＜0.05. The expression ratio of TNF-α mRNA in the Bor group was 1.0± 0. 2, which also significantly lower than that in the Con group (1.3±0.4), P＜0. 05. Conclusion These data suggest that the proteasome inhibitor bortezomib reduces rat hepatocyte injury in the bile duct ligation by mechanisms associated with the inhibition of NF-κB as well as the attenuation of inflammation.