CAJ | 학술논문

目的探讨δ阿片受体激动剂DADLE对脓毒症大鼠肾功能的保护作用及其机制.方法 Sprague-Dawley(SD)大鼠72只,随机(随机数字法)分为假手术组(sham-operated group,SHAM组)、脓毒症组(sepsis group,SEP组)和DADLE处理组(DADLE-treated group,DADLE组),每组24只.SHAM组打开腹腔后关闭,SEP组采用盲肠结扎穿孔(cecal ligation and puncture,CLP)法建立脓毒症模型,DADLE组在CLP后即静脉注射5 mg/kg DALDE.各组在建模后2 h,6 h和10 h各取8只,检测以下指标:①血清尿素氮(BUN)、肌酐(Cr)和β_2-微球蛋白(β_2-MG).②血清肿瘤坏死因子α(TNF-α)和白介素6(IL-6).③左肾组织三磷酸腺苷(ATP)含量.④右肾病理观察.多组间比较用方差分析,组间两两比较采用口检验.结果 ①DADLE组BUN和Cr分别在6 h和10 h比SEP组显著降低(P＜0.01),DADLE组β2-MG在各时间点均显著低于SEP组(P＜0.01).②与SHAM组比较,SEP组和DADLE组在各时间点TNF-α和IL-6均显著升高,DADLE组显著低于SEP组(P＜0.01).③与SHAM组比较,SEP组和DADLE组肾组织的ATP在各时间点均降低(P＜0.01),DADLE组高于SEP组,三组间差异具有统计学意义(P＜0.01).④光镜下见SEP组逐步出现肾小管上皮细胞肿胀、空泡变性、脱落和坏死,基底膜消失,DADLE组的肾小管上皮细胞脱落和坏死程度轻于SEP组,基底膜保持完整.结论 DADLE可以改善脓毒症大鼠肾功能,降低炎症因子水平,减缓肾组织ATP的下降,减轻肾小管上皮细胞的损害,具有肾保护作用.
목적 탐토δ아편수체격동제DADLE대농독증대서신공능적보호작용급기궤제.방법 Sprague-Dawley(SD)대서72지,수궤(수궤수자법)분위가수술조(sham-operated group,SHAM조)、농독증조(sepsis group,SEP조)화DADLE처리조(DADLE-treated group,DADLE조),매조24지.SHAM조타개복강후관폐,SEP조채용맹장결찰천공(cecal ligation and puncture,CLP)법건립농독증모형,DADLE조재CLP후즉정맥주사5 mg/kg DALDE.각조재건모후2 h,6 h화10 h각취8지,검측이하지표:①혈청뇨소담(BUN)、기항(Cr)화β_2-미구단백(β_2-MG).②혈청종류배사인자α(TNF-α)화백개소6(IL-6).③좌신조직삼린산선감(ATP)함량.④우신병리관찰.다조간비교용방차분석,조간량량비교채용구검험.결과 ①DADLE조BUN화Cr분별재6 h화10 h비SEP조현저강저(P＜0.01),DADLE조β2-MG재각시간점균현저저우SEP조(P＜0.01).②여SHAM조비교,SEP조화DADLE조재각시간점TNF-α화IL-6균현저승고,DADLE조현저저우SEP조(P＜0.01).③여SHAM조비교,SEP조화DADLE조신조직적ATP재각시간점균강저(P＜0.01),DADLE조고우SEP조,삼조간차이구유통계학의의(P＜0.01).④광경하견SEP조축보출현신소관상피세포종창、공포변성、탈락화배사,기저막소실,DADLE조적신소관상피세포탈락화배사정도경우SEP조,기저막보지완정.결론 DADLE가이개선농독증대서신공능,강저염증인자수평,감완신조직ATP적하강,감경신소관상피세포적손해,구유신보호작용.
Objective To investigate the effects of δ-opioid receptor ngonist DADLE on renal function of rats with sepsis and the underlying mechanism.Method A total of 72 Sprague-Dawley(SD)rats were randomly divided(random number)into three groups including sham-operated group(SHAM group),sepsis group(SEP group)and DADLE-treated group(DADLE group),eaeh group had 24 rats.Sepsis model was produced by cecal ligation and puncture(CLP).In SHAM group,the abdomen was opened and closed without any other treatment.In DADLE group，DADLE was administered at a dose of 5 mg/kg by intravenous injection after CLP.The following parameters of 8 rats in each group were measured at 2 h,6 h and 10 h.①The serum levels of urea nitrogen(BUN),ereatinine(Ca)and β_2 microglobulin(β_2-MG).②The serum levels of tumor necrosis factor a(TNF-α)and interleukin 6(IL-6).③The contents of adenosine triphosphate(ATP)in left kidneys.④The pathologic changes in fight kidneys.Variance analysis was used in multiple comparison and q test was used to compare between two groups.Results ①Levels of BUN and Cr in DADLE group were lower than those of SEP group at 6 h and 10h,respectively(P＜0.01)，and levels of β2-MG were significantly lower than SEP group at all times(P＜0.01).②Levels of TNF-a and IL-6 of rats both in SEP and DADLE groups were significantly higher than those SHAM group(P＜0.01),and both these parameters in DADLE group were significantly lower than those SEP group (P＜0.01).③Levels of ATP both in DADLE and SEP groups were decreased compared with SHAM group,and ATP in DADLE group were higher than that d SEP group.The differences were significant in the three groups(P＜0.01).④The hydropic,Maune degeneration and necrobiosis in tubular epithelial cells and disapperance of basement membrane could be seen step by step in SEP group,and DADLE group was better than SEP group.Conclusions Deaung with DADLE on rats with sepsis can improve the renal function,reduce the level of cytokines and the decline of ATP contents in renal tissue,alleviate the pathological changes of renal tubular,above all,DADLE has renal protective effects on rats with sepsis.