TRPV4受体对血管紧张素Ⅱ诱导的小鼠肾损害的影响

目的通过利用瞬时受体电位香草酸亚型4(transient receptor potential vanilloid type 4,TRPV4)基因敲除(TRPV4-/-)小鼠,探讨TRPV4受体在血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)所诱导的肾损害中的作用。方法实验小鼠分为假手术组和Ang Ⅱ处理组。在野生型和TRPV4-/-小鼠中通过皮下灌注Ang Ⅱ建立Ang Ⅱ依赖型高血压模型,而假手术组小鼠皮下只灌注生理盐水。处理4周后,分别检测小鼠的尾动脉收缩压、24 h尿白蛋白排泄量及8-异构前列腺素、血清肌酐的改变,并且同时对肾组织病理学的变化进行分析。结果与相应的假手术组比较,Ang Ⅱ处理组小鼠血压升高、尿白蛋白及8-异构前列腺素排泄量增加,并同时伴有血清肌酐升高(P0.05);肾小球纤维样硬化及肾小管间质损伤程度均出现明显加重,并伴有肾胶原蛋白水平的增高(P0.05)。除血压外,TRPV4基因敲除能显著抑制上述所有病理变化,从而缓解Ang Ⅱ所诱导的肾损害(P0.05)。结论在Ang Ⅱ所诱导高血压的过程中,TRPV4基因敲除能够明显减弱由上述过程所诱发的肾损害。因此,上述研究结果提示TRPV4受体在促进Ang Ⅱ所诱导的肾损害中发挥重要的病理生理学作用。

Effect of TRPV4 on angiotensin II-induced renal injury in mice

Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4 (TRPV4) on angiotensin II (Ang II)-induced renal injury in TRPV4-null mutant (TRPV4 ^{- / -} ) mice. Methods The mice were divided into sham group and Ang II-treated group. Ang II was infused systemically into wild type (WT) and TRPV4 ^{- / -} mice via a miniosmotic pump for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, serum creatinine, and the pathological changes in the kidney tissues were assayed after the 4-week treatment. Results Compared with corresponding sham mice, Ang II infusion led to enhanced systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, increased serum creatinine (P< 0.05), and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index (P < 0.05) in the WT and TRPV4 ^{- / -} mice. The result were associated with enhanced collagen levels in the kidney (P < 0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure (P < 0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang II-induced hypertension, suggesting that TRPV4 may contribute to the pathophysiology of angiotensin II-induced renal injury.