表皮生长因子对肾缺血再灌流修复的影响

The Effects of Epidermal Growth Factor on the Repair of Renal Ischemia and Reperfusion

探讨肾缺血再灌流损伤修复过程中颌下腺、胰腺、肾脏产生的表皮生长因子（ＥＧＦ）的作用及作用机制。方法选用大鼠右肾切除、左肾缺血６０ｍｉｎ继之再灌流不同时间模型，观察颌下腺切除后对肾功能和形态恢复的影响。用免疫组化和ＷｅｓｔｅｒｍＢｌｏｔ方法观察肾缺血再灌流损伤修复过程中肾组织增殖细胞核抗原（ＰＣＮＡ），胰腺、颌下腺、肾脏和血清ＥＧＦ以及肾组织ＥＧＦ受体（ＥＧＦＲ）表达的变化。结果颌下腺切除后，损伤后的肾功能和肾组织形态结构恢复到正常的时间明显延长。ＰＣＮＡ免疫组化显示，６０ｍｉｎ肾缺血再灌流２４ｈ出现再生，再灌流３ｄ再生修复达到高峰，再灌流７ｄ基本消失。与此相对应，颌下腺、胰腺在再灌流１、３ｄ时ＥＧＦ表达明显增强，血清ＥＧＦ含量增多，肾组织ＥＧＦＲ表达明显增强；再灌流７ｄ时，颌下腺、胰腺ＥＧＦ表达、血清ＥＧＦ含量及肾组织ＥＧＦＲ表达均基本恢复正常。结论颌下腺、胰腺所产生的ＥＧＦ在损伤后肾小管上皮的修复中可能起重要作用。

Purpose The protective effects and mechanisms of endogenous epidermal growth factor(EGF)(secreated by submandibular gland,pancreas and kidney)on renal function and structure during the injury and repair of renal ischemia and reperfusion. Methods Using renal ischemia model with right nephrectomy and occlusion of the left renal pedical for 60 minute followed by different reperfusion time,we observed the effects of sialoadenectomy on the recovery of the injureded renal function and morphology.Immunohistochemical staining and Wes tern Blot technique were employed to detect the expression of prolifering cell nuclear antigen(PCNA)in the renal tissue,the expression changes of EGF in the pancreas,submandibulargland,kidney and serum and the expression of EGF receptor ( EGFR ) in the renal tissue during the injury and repair of renal ischemia and reperfusion. Results The sialoadenectomy can markedly retarded the recovery of injured renal function and structure. PCNA immunohistochemical staining revealed that after 60 minute ischemia and 24 hour reperfusion,regeneration appeared in the damaged renal tubule.On the 3rd day of reperfusion,the peak of regeneration approached.On the 7th day of reperfusion,the regeneration almost disappeared in the renal tissue.In correspondence with all those changes above,on the 1st and 3rd day reperfusion after 60 minute renal ischemia,the pancreas and submandibular gland strengthened the expression of EGF.The serum EGF level increased markedly.The expression of EGFR in the renal tissue enhanced significantly.On the 7th day of reperfusion,the expression of EGF in the pancreas and submandibular gland,the content of serum EGF and the expression of EGFR in the renal tissue, all restored to the normal level. Conclusions The EGF secreated from submaxillary gland and pancreas may play animportant role in the repair of injured renal tubule epithelia.EGF may accelerate the repair of injured renal tubule epithelia through the mechanisms mediated by the EGFR.