非诺贝特预处理对肾缺血再灌注损伤小鼠的保护作用

Fenofibrate Pretreatment Ameliorates Kidney Ischemia Reperfusion Injury

关键词:  非诺贝特  肾缺血再灌注损伤  凋亡  JAK2/STAT3

Key words:  fenofibrate  renal ischemia reperfusion injury  apoptosis  JAK2/STAT3

摘要:

目的 探讨非诺贝特(fenofibrate，FENO)预处理对小鼠肾缺血再灌注损伤的保护作用及其机制。方法 建立小鼠肾缺血再灌注损伤模型。24只C57BL/6小鼠，♂，随机分为3个组(n=8)，分别为假手术组(Sham组)、肾缺血再灌注损伤模型组(IRI组)和非诺贝特预处理组(FENO组)。Sham组、IRI组和FENO组经不同方法处理后，经PAS染色观察肾脏病理学形态学变化，Western blot检测JAK2和 STAT3，p-JAK2，p-STAT3，Caspase 3表达情况。结果 与Sham组相比，IRI组血清肌酐和血尿素氮水平明显升高，病理检查可见肾脏内肾小管上皮细胞肿胀坏死变多、蛋白管型形成明显，还可观察到炎症细胞浸润增加显著；Western blot显示p-JAK2和p-STAT3，蛋白表达量均明显增加，JAK2和STAT3表达无明显变化，但Caspase 3 表达显著减少。与IRI组相比，FENO组血清肌酐和血尿素氮量明显下降，肾小管上皮细胞肿胀坏死减轻，炎症细胞浸润变少、蛋白管型形成减少，p-JAK2和p-STAT3表达明显降低，Caspase 3表达增加，JAK2和STAT3表达无明显变化。结论 FENO预处理小鼠可通过抑制JAK2/STAT3信号通路的激活从而减少肾小管上皮细胞凋亡，进而减轻肾缺血再灌注损伤。

Abstract:

OBJECTIVE To investigate potential protection and mechanism of fenofibrate on renal ischemia reperfusion injury. METHODS All of 24 male C57BL/6 mice were randomly divided into three groups: Sham group, kidney ischemia reperfusion injury group(IRI group), and fenofibrate pretreatment group(FENO group). The mice in IRI group and Sham group were treated by different methods. Then the pathology of renal tissues was observed according to PAS staining and the protein level of JAK2, STAT3, p-JAK2, p-STAT3 and Caspase 3 were measured by Western blot. RESULTS Compared with the Sham group, the serum levels of Cr and BUN in IRI group were significantly higher. Moreover, renal tubular necrosis, protein tube formation, inflammatory cell infiltration, and the protein expression level of p-JAK2 p-STAT3 were significantly increased as well as the expression of Caspase 3 was significantly reduced, but the protein expression level of JAK2 and STAT3 had no difference. However, compared with the IRI group, the serum levels of Cr and BUN in FENO group were significantly reduced. Moreover, renal tubular necrosis, protein tube formation, inflammatory cell infiltration, and the protein expression level of p-JAK2 , p-STAT3 were decreased as well as the expression of Caspase 3 was significantly increased, but the protein expression level of JAK2 and STAT3 still had no difference. CONCLUSION Fenofibrate pretreatment ameliorates renal ischemia reperfusion injury by reducing apoptosis though inhibiting activating JAK2/STATA3 signal pathway.