【作者】 毛渭东；

【导师】 孙少华；

【作者基本信息】 兰州大学 ， 病理与病理生理学， 2008， 硕士

【摘要】 目的探讨乌司他丁(ulinastatin,UTI)在大鼠肾脏机械性损伤后对肾脏白细胞介素6(Interleukin-6,IL-6)和热休克蛋白70(Heat shock protein70,HSP70)表达的影响及意义。方法成年雌性Wistar大鼠66只,随机分为非创伤对照组(C组)、单纯创伤组(T组)、创伤后给予乌司他丁组(U组)。后两组动物分别与创伤后1h、6h、12h、24h、36h各处死六只。采用自由落体生物撞击仪撞击大鼠脊肋角复制创伤动物模型。HE染色观察损伤后肾脏的基本病理改变。用组织芯片技术及免疫组织化学方法检测各组创伤后1 h、6 h、12 h、24 h、36 h点肾脏组织中IL-6和HSP70蛋白的表达。结果对照组肾脏组织中IL-6和HSP70蛋白均呈弱阳性表达。与对照组比较,单纯创伤组在创伤后1、6、12、24 h点IL-6表达明显增强(P＜0.05),6 h点HSP70表达明显增强(P＜0.05),各时相点Paller评分均升高(P＜0.05)。创伤后注射乌司他丁组各时相点肾组织中IL-6表达明显低于单纯创伤组(P＜0.05),HSP70表达在1、24、36 h点明显高于单纯创伤组(以1 h点为著,P＜0.05),且创伤后各时相点Paller评分均降低(P＜0.05)。Spearman等级相关分析显示:单纯创伤组HSP70表达与IL-6表达呈正相关(P＜0.05);创伤后注射乌司他丁组HSP70表达与IL-6表达呈负相关(P＜0.01)。结论1、急性创伤后早期肾脏IL-6的表达水平反映了肾小管上皮细胞的损伤及其炎性反应程度。2、IL-6在调节炎症方面具有双重功能,在发挥炎性损伤作用的同时,又通过其炎性刺激作用诱导肾小管上皮细胞表达HSP70发挥抗炎作用。3、在无外源性药物干预的情况下,机体自身经抗炎作用而产生的HSP70,在单纯性创伤早期没有对肾脏起到有效的保护作用。4、急性创伤后12小时至36小时,乌司他丁通过上调肾小管上皮细胞HSP70的再次高表达以保护肾脏的缺血再灌注损伤。5、乌司他丁主要在创伤后早期(以1小时为著)发挥作用,通过抑制肾小管上皮细胞IL-6的过度表达,上调HSP70的表达,纠正两者表达水平之间的比例失衡,而对大鼠肾脏起到有效的保护作用。更多还原

【Abstract】 OBJECTIVE To investigate the significance of ulinastatin’s effects on expression of IL-6 and HSP70 in kidney after mechanical injury.METHODS Sixity-six adult female Wistar rats were randomly divided into three groups:control(C,n=6),trauma(T,n=30),and injected ulinastatin after trauma(U,n=30).The 6 rats in the last two groups were excuted at 1h,6h,12h,24h and 36h after trauma respectively.The model of trauma rats was made with free-fall bio-impactor striking the spinal column and ribs of rats.Renal tissue was observed after HE stained. The expression of IL-6 and HSP70 in each group’s renal tissue were detected with tissue chip and immunohistochemical stain at 1,6,12,24 and 36 h after trauma.RESULTS The expression of IL-6 and HSP70 in renal tissue was low in control group.Compared with control,the expression of IL-6 in trauma group was markedly increased at 1,6,12,24 h after trauma(P＜0.05),the expression of HSP70 was significantly increased at 6h after trauma (P＜0.05),injury score heightend correspondly(P＜0.05).The expression of IL-6 in group injected Ulinastatin after trauma were more lower than trauma group,the expression of HSP70 at 1,24,36 h after trauma was higher than trauma group especially at 1 h(P＜0.05),meanwhile,injury score decreased correspondly(P＜0.05).The Spearman correlation analyse revealed that in group T the expression between HSP70 and IL-6 present positive correlation(P＜0.05),but in group U the expression between HSP70 and IL-6 present negative correlation(P＜0.01).CONCLUSION 1.IL-6 expression at early times after trauma can reflex the level of injury and inflammatory reaction of renal tissue. 2.IL-6 have dual effects on adjust inflammation.It not only lead to the inflammatory injury,but also induce HSP70 expression of renal tubular epithelial cell to produce anti-inflammatory effects through its inflammatory excitation.3.Without exogenous medicine’s intervention, the HSP70 produced by organism itself have not play a effective protection part in against inflammatory injury at early times after trauma.4.From 12h to 36h after trauma,Ulinastatin can reduce the risk of Ischemia reperfusion injury through up-regulation of HSP70 expression. 5.Ulinastatin can reduce the risk of renal injury at early times after trauma especially at 1 hour.The protective effects of ulinastatin associated with the decrease of IL-6 expression,up-regulation of HSP70 expression,and recitify the unbalanced proportion between HSP70 and IL-6 expression.更多还原