CAJ | 학술논문

目的探讨高迁移率族蛋白B1（high mobility group box 1， HMGB1）在脓毒症大鼠肠道损伤中的作用及丙酮酸乙酯对脓毒症肠道损伤保护作用的机制。方法采用盲肠结扎穿孔术（ cecal ligation and puncture， CLP）建立脓毒症大鼠模型。60只SD大鼠随机分为假手术组（ S组）、脓毒症组（C组）和丙酮酸乙酯治疗组（M组），每组20只。 M组于术后即刻腹腔注射丙酮酸乙酯溶液（40mg k／g ），S组及C组注射等量乳酸钠林格液。各实验组于术后3、6、12、24 h随机处死5只大鼠，光镜下观察肠道损伤情况，进行小肠组织病理评分，检测血浆二胺氧化酶（ diamine oxidase， DAO）及D －乳酸浓度，采用免疫组织化学法和逆转录－聚合酶链反应法（ reverse transcription－PCR， RT－PCR）检测小肠组织HMGB1表达。结果 S组各检测指标在各时间点比较差异无统计学意义。 C组及M组各检测指标均随时间延长呈升高趋势。 C组小肠组织病理评分、C组和M组小肠组织HMGB1表达在6、12、24 h均高于S组（P＜0．05），M组小肠组织病理评分在12、24 h高于S 组（P＜0．05），C组和M组血浆DAO及D－乳酸浓度在各时间点均高于S组（ P＜0．05）。 M组小肠组织病理评分在24 h低于C组，HMGB1 mRNA表达、血浆DAO及D－乳酸浓度在6、12、24 h均低于C组，小肠组织HMGB1蛋白含量在12、24 h低于C组（P＜0．05）。结论脓毒症大鼠肠道损伤程度与肠组织表达 HMGB1相关。丙酮酸乙酯可减轻脓毒症肠道损伤，其机制可能与抑制肠组织HMGB1表达有关。
목적탐토고천이솔족단백B1（high mobility group box 1， HMGB1）재농독증대서장도손상중적작용급병동산을지대농독증장도손상보호작용적궤제。방법채용맹장결찰천공술（ cecal ligation and puncture， CLP）건립농독증대서모형。60지SD대서수궤분위가수술조（ S조）、농독증조（C조）화병동산을지치료조（M조），매조20지。 M조우술후즉각복강주사병동산을지용액（40mg k／g ），S조급C조주사등량유산납림격액。각실험조우술후3、6、12、24 h수궤처사5지대서，광경하관찰장도손상정황，진행소장조직병리평분，검측혈장이알양화매（ diamine oxidase， DAO）급D －유산농도，채용면역조직화학법화역전록－취합매련반응법（ reverse transcription－PCR， RT－PCR）검측소장조직HMGB1표체。결과 S조각검측지표재각시간점비교차이무통계학의의。 C조급M조각검측지표균수시간연장정승고추세。 C조소장조직병리평분、C조화M조소장조직HMGB1표체재6、12、24 h균고우S조（P＜0．05），M조소장조직병리평분재12、24 h고우S 조（P＜0．05），C조화M조혈장DAO급D－유산농도재각시간점균고우S조（ P＜0．05）。 M조소장조직병리평분재24 h저우C조，HMGB1 mRNA표체、혈장DAO급D－유산농도재6、12、24 h균저우C조，소장조직HMGB1단백함량재12、24 h저우C조（P＜0．05）。결론농독증대서장도손상정도여장조직표체 HMGB1상관。병동산을지가감경농독증장도손상，기궤제가능여억제장조직HMGB1표체유관。
Objective To investigate the role of high mobility group box 1 ( HMGB1 ) in intestinal tract injury of sepsis in rats and the mechanism of its treatment with ethyl pyruvate.Methods A rat sepsis model was established by cecal ligation and puncture ( CLP ) .Sixty SD rats were randomly divided into the sham group (Group S), sepsis group (Group C)and ethyl pyruvate treated group ( Group M) with 20 rats in each group.Group M received intraperitoneal injection of ethyl pyruvate ( 40 mg/kg ) immediately after operation, while Group S and Group C were both given intraperitoneal injection of Lactated Ringer's Solution.Five rats in each group were picked up at 3, 6, 12, 24 h after CLP to have intestinal tract pathological damage observed by microscope, and the plasma levels of diamine oxidase ( DAO) and D-lactic acid measured, and the HMGB1 expression of small intestinal tissues detected by immunohistochemical method and reverse transcription -polymerase reaction method ( RT-PCR) .Results There was no significant difference at each time point of each detection index in Group S.In Group C and Group M, each detection index was rising with increased postoperative time.The intestinal histological scores of Group C, the HMGB1 expression of small intestinal tissues of Group C and M were higher than that of Group S at 6, 12, 24 h,while in Group M , the scores were higher than that of Group S at 12, 24 h (P<0.05).The plasma levels of diamine oxidase ( DAO) and D-lactic acid of Group C and M were higher than those of Group S at each time point.Compared with Group C, the intestinal histological scores of Group M were lower at 24 h, and the expression level of HMGB1 mRNA and the plasma levels of DAO and D-lactic acid were lower at 6, 12, 24 h, and the expression of HMGB1 protein in small intestinal tissue was lower at 12, 24 h ( P<0.05).Conclusion The degree of intestinal tract injury was associated with the HMGB1 expression of intestinal tissues.Ethyl pyruvate could reduce sepsis-induced intestinal tract injury, which was likely due to the inhibition of HMGB1 expression in intestinal tissues.