CAJ | 학술논문

目的：探讨硫化氢（H2 S）在重症急性胰腺炎（SAP）中的作用及机制。方法 SD大鼠分为对照组（n＝6）、SAP组（n＝10）、炔丙基甘氨酸（PAG）＋SAP组（n＝10）、5 mg/kg NaHS＋SAP组（n＝10）、10 mg/kg NaHS＋SAP组（n＝10）、20 mg/kg NaHS＋SAP组（n＝10）、100 mg/kg NaHS＋SAP组（n＝10）、wortmannin （以下简写W）＋SAP组（n＝10）、5 mg/kg NaHS ＋W＋SAP组（n＝10）及100 mg/kg NaHS ＋W＋SAP组（n＝10），腹腔内注射6％左旋精氨酸制作SD大鼠SAP模型，24 h后处死大鼠。ELISA法检测血浆IL-6水平、胰腺髓过氧化物酶（MPO）活性，Western blot法检测各组大鼠胰腺磷酸化丝/苏氨酸蛋白激酶（p-AKT）及核因子抑制蛋白-κB（IκBα）表达水平，EMSA法检测核转录因子-κB（NF-κB）活性。结果 SAP组和PAG＋SAP组血浆IL-6水平、胰腺组织MPO活性及p-AKT水平较对照组明显升高（P＜0．05），NF-κB活性也得到增强，且PAG＋ SAP组高于SAP组（P＜0．05）；而SAP组和 PAG＋ SAP组 IκBα水平较对照组明显降低（P＜0．05），且 PAG＋ SAP组低于 SAP组（P＜0．05）。给予不同剂量NaHS后，各组血浆IL-6水平、胰腺组织MPO活性、p-AKT水平及NF-κB活性随着NaHS浓度升高而逐渐降低；IκBα水平却逐渐升高。给予W后，各组血浆IL-6、胰腺MPO活性及p-AKT水平均明显降低，NF-κB活性有一定程度的减弱，而IκBα表达水平明显升高。结论外源性 H2 S可减轻SAP的炎症程度，且该作用在一定范围内与血浆 H2 S水平呈正比。H2 S通过介导PI3K/AKT-NF-κB通路能减轻SAP胰腺损伤的炎症程度。
목적：탐토류화경（H2 S）재중증급성이선염（SAP）중적작용급궤제。방법 SD대서분위대조조（n＝6）、SAP조（n＝10）、결병기감안산（PAG）＋SAP조（n＝10）、5 mg/kg NaHS＋SAP조（n＝10）、10 mg/kg NaHS＋SAP조（n＝10）、20 mg/kg NaHS＋SAP조（n＝10）、100 mg/kg NaHS＋SAP조（n＝10）、wortmannin （이하간사W）＋SAP조（n＝10）、5 mg/kg NaHS ＋W＋SAP조（n＝10）급100 mg/kg NaHS ＋W＋SAP조（n＝10），복강내주사6％좌선정안산제작SD대서SAP모형，24 h후처사대서。ELISA법검측혈장IL-6수평、이선수과양화물매（MPO）활성，Western blot법검측각조대서이선린산화사/소안산단백격매（p-AKT）급핵인자억제단백-κB（IκBα）표체수평，EMSA법검측핵전록인자-κB（NF-κB）활성。결과 SAP조화PAG＋SAP조혈장IL-6수평、이선조직MPO활성급p-AKT수평교대조조명현승고（P＜0．05），NF-κB활성야득도증강，차PAG＋ SAP조고우SAP조（P＜0．05）；이SAP조화 PAG＋ SAP조 IκBα수평교대조조명현강저（P＜0．05），차 PAG＋ SAP조저우 SAP조（P＜0．05）。급여불동제량NaHS후，각조혈장IL-6수평、이선조직MPO활성、p-AKT수평급NF-κB활성수착NaHS농도승고이축점강저；IκBα수평각축점승고。급여W후，각조혈장IL-6、이선MPO활성급p-AKT수평균명현강저，NF-κB활성유일정정도적감약，이IκBα표체수평명현승고。결론외원성 H2 S가감경SAP적염증정도，차해작용재일정범위내여혈장 H2 S수평정정비。H2 S통과개도PI3K/AKT-NF-κB통로능감경SAP이선손상적염증정도。
Objective To explore the role and mechanism of H2 S in severe acute pancreatitis .Methods SD rats were randomly assigned into several experimental groups :contorl group(n=6) ,SAP group(n=10) ,PAG+SAP group(n=10) ,5 mg/kg NaHS+SAP group(n=10) ,10 mg/kg NaHS+SAP group(n=10) ,20 mg/kg NaHS+SAP group(n=10) ,100 mg/kg NaHS+SAP group (n=10) ,wortmannin(W)+ SAP group(n= 10) ,5 mg/kg NaHS + W+ SAP group(n=10) and 100 mg/kg NaHS+ W+ SAP group(n=10) .These rats were intra-peritoneal injected L-Arginine to get SAP model ,and sacrificed ar 24 h hour after the first in-jection .Plasma IL-6 and MPO activity in pancreas were determined by ELISA .Expression of p-AKT and IκBαin pancreas were de-tected by Western blot ,and NF-κB activity was assessed with EMSA .Results SAP and PAG+ SAP resulted in a significant in-creasing in plasma IL-6 ,MPO activity and expression of p-AKT in pancreas ,when compared with the control group(P<0 .05) ,and NF-κB activity also increased ,and NF-κB activity in PAG+SAP group was more significant (P<0 .05);however ,IκBαexpression in SAP and PAG+SAP down-regulated obviously ,when compared with the control group(P<0 .05) ,and the expression in PAG+SAP group was significantly lower(P<0 .05) .Different dosage of NaHS reduced that the level of plasma IL-6 ,MPO activity ,ex-pression of p-AKT and NF-κB activity in pancreas changed in different degrees ,yet IκBαexpression in these groups increased gradu-ally .When compared with the SAP group ,5 mg/kg NaHS+SAP and 100 mg/kg NaHS+SAP ,plasma IL-6 ,MPO activity and ex-pression of p-AKT in pancreas significantly depressed after given wortmannin ,besides NF-κB activity also down-regualated;never-theless IκBαexpression up-regulated .Conclusion H2 S in precondition induced the development of an anti-inflammatory activity in SAP ,and in proportion with the concentration of H2 S in blood in a degree .H2 S regulated the degree of SAP injury via PI3K/AKT-NF-κB pathway .