中西医结合肝病杂志
中西醫結閤肝病雜誌
중서의결합간병잡지
CHINESE JOURNAL OF INTEGRATED TRADITIONAL AND WESTERN MEDICINE ON LIVER DISEASES
2015年
2期
95-98
,共4页
曹承楼%孙克伟%胡莉%陈斌
曹承樓%孫剋偉%鬍莉%陳斌
조승루%손극위%호리%진빈
肝功能衰竭%树突状细胞%凋亡%生长停滞特异性基因 6%Axl%茵陈蒿汤/药效学
肝功能衰竭%樹突狀細胞%凋亡%生長停滯特異性基因 6%Axl%茵陳蒿湯/藥效學
간공능쇠갈%수돌상세포%조망%생장정체특이성기인 6%Axl%인진호탕/약효학
liver failure%dendretic cells%apoptosis%growth arrest-specific protein 6%Axl%Yinchenhao decoction/pharmacodynamics%rats
目的：研究茵陈蒿汤对慢加急性肝衰竭（ACLF）模型大鼠肝内树突状细胞（DC）凋亡的影响及其与 Axl 信号的关系。方法：采用牛血清白蛋白致敏建立免疫性肝纤维化大鼠模型，然后用 D－氨基半乳糖加脂多糖攻击建立 ACLF 模型，同时给予茵陈蒿汤灌胃治疗；观察攻击前及攻击后1h、12h 其血清肝功能及肝脏组织病理学变化，应用 CD11c／CD123＋TUNEL 凋亡双染色、CD11c／CD123＋Axl－mRNA 原位杂交双染色检测 DC 的凋亡及 DCAxl 的基因表达。结果：模型组大鼠表现为明显的肝纤维化基础上出现急性肝损伤，中药茵陈蒿汤组则炎症反应减轻，在攻击后1h、12h 均显示有抑制树突状细胞凋亡的作用。正常组 DC 的 Axl－mRNA 表达水平较高，而模型组大鼠随着肝纤维化、肝衰竭的发展，Axl 表达水平下降明显，茵陈蒿汤则具有上调 DC 的 Axl 表达的作用。 DC 凋亡指数与 Axl－mRNA 的表达呈线性负相关。结论：①肝内 DC 在由慢性肝病发展为 ACLF 进程中，其细胞凋亡增加可能是炎症活动不能控制，免疫修复障碍的重要原因。②Gas6／Axl 通道是调控 DC 凋亡的重要机制。 Axl 信号可抑制 DC 凋亡。③茵陈蒿汤可上调Axl 表达，抑制 DC 凋亡，这可能是其调节 ACLF 的免疫强度的重要机制。
目的：研究茵陳蒿湯對慢加急性肝衰竭（ACLF）模型大鼠肝內樹突狀細胞（DC）凋亡的影響及其與 Axl 信號的關繫。方法：採用牛血清白蛋白緻敏建立免疫性肝纖維化大鼠模型，然後用 D－氨基半乳糖加脂多糖攻擊建立 ACLF 模型，同時給予茵陳蒿湯灌胃治療；觀察攻擊前及攻擊後1h、12h 其血清肝功能及肝髒組織病理學變化，應用 CD11c／CD123＋TUNEL 凋亡雙染色、CD11c／CD123＋Axl－mRNA 原位雜交雙染色檢測 DC 的凋亡及 DCAxl 的基因錶達。結果：模型組大鼠錶現為明顯的肝纖維化基礎上齣現急性肝損傷，中藥茵陳蒿湯組則炎癥反應減輕，在攻擊後1h、12h 均顯示有抑製樹突狀細胞凋亡的作用。正常組 DC 的 Axl－mRNA 錶達水平較高，而模型組大鼠隨著肝纖維化、肝衰竭的髮展，Axl 錶達水平下降明顯，茵陳蒿湯則具有上調 DC 的 Axl 錶達的作用。 DC 凋亡指數與 Axl－mRNA 的錶達呈線性負相關。結論：①肝內 DC 在由慢性肝病髮展為 ACLF 進程中，其細胞凋亡增加可能是炎癥活動不能控製，免疫脩複障礙的重要原因。②Gas6／Axl 通道是調控 DC 凋亡的重要機製。 Axl 信號可抑製 DC 凋亡。③茵陳蒿湯可上調Axl 錶達，抑製 DC 凋亡，這可能是其調節 ACLF 的免疫彊度的重要機製。
목적：연구인진호탕대만가급성간쇠갈（ACLF）모형대서간내수돌상세포（DC）조망적영향급기여 Axl 신호적관계。방법：채용우혈청백단백치민건립면역성간섬유화대서모형，연후용 D－안기반유당가지다당공격건립 ACLF 모형，동시급여인진호탕관위치료；관찰공격전급공격후1h、12h 기혈청간공능급간장조직병이학변화，응용 CD11c／CD123＋TUNEL 조망쌍염색、CD11c／CD123＋Axl－mRNA 원위잡교쌍염색검측 DC 적조망급 DCAxl 적기인표체。결과：모형조대서표현위명현적간섬유화기출상출현급성간손상，중약인진호탕조칙염증반응감경，재공격후1h、12h 균현시유억제수돌상세포조망적작용。정상조 DC 적 Axl－mRNA 표체수평교고，이모형조대서수착간섬유화、간쇠갈적발전，Axl 표체수평하강명현，인진호탕칙구유상조 DC 적 Axl 표체적작용。 DC 조망지수여 Axl－mRNA 적표체정선성부상관。결론：①간내 DC 재유만성간병발전위 ACLF 진정중，기세포조망증가가능시염증활동불능공제，면역수복장애적중요원인。②Gas6／Axl 통도시조공 DC 조망적중요궤제。 Axl 신호가억제 DC 조망。③인진호탕가상조Axl 표체，억제 DC 조망，저가능시기조절 ACLF 적면역강도적중요궤제。
Objective:To observe the effects of Yinchenhao decoction on dendretic cells’(DC) apoptosis of acute-on-chronic liver fail-ure (ACLF) rats and find out its relationship with Axl signal.Methods:Immunological hepatic fibrosis was induced by administration of bo-vine serum albumin to Wistar rats.D-galactosamine and lipopolysaccharide were simultaneously intraperitoneally injected to establish the ACLF models.Yinchenhao decoction was dosed as treatment to the rats.Serum levels of liver function tests were detected on the time before the acute attack and 1 hour, 12 hours after the acute attack.Liver HE staining was carried out to examing liver fibrosis and necrosis.CD11c/CD123 +Tunel apoptosis double staining was established to detecte apoptosis of DC, and CD11c/CD123 +Axl-mRNA in situ hybridization double staining to detect Axl expression of DC.Results:Acute liver injury on the bosis of fibrosis was observed obviously in the model rats, inflammatory reaction wasalleviated in Yinchenhao decoction group.Yinchenhao decoction could depress apoptosis of DC on the time of 1 and 12 hours after acute attack.Axl-mRNA expression levels were high in the normal rats , and slided down obviously in the developing course of liver fibrosis and failure.When a correlation analysis of the DCs’ apoptotic index with mean optical density of Axl-mRNA expression of corre-sponding slices was carried out, linear negative correlation was found out.Conclusions:①Apoptosis of liver dendretic cells increase in the course of chronic liver diseas developing to acute-on-chronic livser failure.This may be the important reason of inflammation incontrollablilty and immune repair disability.②Gas6 /Axl signal pathway is a important mechanism to regulate DCs’ apoptosis.Axl signal could depress DCs’ apoptosis.③Yinchenhao decoction could upregulated Axl expression to depress DCs’ apoptosis.It would be the important mechanism of its regulating immune intensity in ACLF.
