Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats
Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats
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DOI：
10.1152/ajpregu.90460.2008
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发表时间：
2009-02-01
影响因子：
2.8
通讯作者：
Cunningham, J. Thomas
中科院分区：
文献类型：
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作者：
Carreno, Flavia Regina;Ji, Lisa L.;Cunningham, J. Thomas
Carreno FR，Ji LL，Cunningham JT.改变的中央TRPV 4表达和脂筏协会相关的不适当的加压素分泌在阿尔茨海默病大鼠。Am J Physiol Regul Integr Comp Physiol 296：R454-R466，2009。首次发表于2008年12月17日; doi：10.1152/ajpregu.90460.2008。加压素（AVP）释放不当导致稀释性低钠血症在许多病理生理状态，如肝硬化。介导AVP不适当释放的中心分子机制尚不清楚。我们测试的假设，在中枢神经系统中的表达或运输的TRPV 4的变化可能会导致不适当的AVP释放在胆管结扎（BDL）模型的肝硬化大鼠。手术后4周，BDL大鼠表现出血浆加压素和血浆肾素活性（PRA）显著增加，血容量过多，血浆渗透压降低。这些作用通过给BDL大鼠提供2%的盐水饮用15天来阻断。TRPV 4蛋白表达在来自含有下丘脑视上核（SON）的BDL大鼠的脑穿孔中显著增加（100% +/- 11至157% +/- 4.8），并且这种作用在给予盐水的BDL大鼠中被阻断。免疫组化显示BDL大鼠SON中TRPV 4阳性细胞和AVP神经元的百分比也显著增加。在BDL大鼠的下丘脑中，与假手术组相比，TRPV 4脂筏结合增加（从100% +/- 2.1增加到326.1% +/- 16）。在给予2%生理盐水饮用的BDL大鼠中，该效应显著减弱（174% +/- 11）。在脑干中，BDL减少了TRPV 4脂筏结合，并且与血浆AVP和PRA呈负相关。我们推测，TRPV 4的表达和脂筏内区室化的变化可能有助于肝硬化AVP释放相关的前馈机制。
Carreno FR, Ji LL, Cunningham JT. Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats. Am J Physiol Regul Integr Comp Physiol 296: R454-R466, 2009. First published December 17, 2008; doi: 10.1152/ajpregu.90460.2008.-Inappropriate vasopressin (AVP) release causes dilutional hyponatremia in many pathophysiological states such as cirrhosis. The central molecular mechanisms that mediate inappropriate AVP release are unknown. We tested the hypothesis that changes in the expression or trafficking of TRPV4 in the central nervous system may contribute to inappropriate AVP release in the bile duct ligation (BDL) model of cirrhosis in the rat. Four weeks after surgery, BDL rats demonstrated significantly increased plasma vasopressin and plasma renin activity (PRA), hypervolemia, and decreased plasma osmolality. These effects were blocked by providing BDL rats with 2% saline to drink for 15 days. TRPV4 protein expression was significantly increased in brain punches from BDL rats containing the supraoptic nucleus (SON) of the hypothalamus (100% +/- 11 to 157% +/- 4.8), and this effect was blocked in BDL rats given saline. Immunohistochemistry demonstrated a significant increase in TRPV4-positive cells and the percentage of AVP neurons that also were TRPV4-positive in the SON of BDL rats. In the hypothalamus of BDL rats, TRPV4 lipid raft association increased compared with sham (from 100% +/- 2.1 to 326.1% +/- 16). This effect was significantly attenuated in BDL rats given 2% saline to drink (174% +/- 11). In the brain stem, TRPV4 lipid raft association was reduced by BDL and inversely related to plasma AVP and PRA. We speculate that changes in TRPV4 expression and compartmentalization within lipid rafts could contribute to a feed-forward mechanism related to AVP release in cirrhosis.