Mechanism by which dietary protein moduletes renal hemodyr-amies

膳食蛋白质调节肾血红蛋白的机制

• 批准号: 03670262
• 负责人: YANAGISAWA Hiroyuki
• 金额: $ 1.28万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670262/
• 关键词: Glomerulus; Dietary protein; Phospholipase; Cyclooxygenase; Eicosanoid; G-protein; Gープロテイン; サイクロオキシゲナ-ゼ; ホスホリパ-ゼ; 蛋白食

High protein intake increases glomerular filtration rate (GFR) and renal plasma flow. To elucidate the molecular mechanisms, we examined the production of eicosanoids, the activities of phosphatidylethanolamine (PE)-specific phospholipase A_2 (PLA_2) and cyclooxygenase and the mass of G-protein subunits (G_<alphas>, G_<alphai2>, G_<alphai3>, and G_<beta>) in glomeruli isolated from rats fed a low (6% casein) or high (40% casein) protein diet for approximately 8 weeks. Glomeruli isolated from high protein-fed rats produced significantly greater amounts of PGE_2, 6-keto PGF_<1alpha>, and TxB_2 than glomeruli isolated from low protein-fed rats with increased activities of PE-specific PLA_2 and cyclooxygenase. Compared to rats fed a low protein diet a decrement in glomerular G_<alphai2> and G_<alphai3> and an increment in glomerular G_<beta> were observed in rats fed a high protein diet. Also these changes seen in rats fed a high protein diet were restored to the levels comparable to those observed in rats fed a low protein diet by pretreating the rats with the angiotensin converting enzyme inhibitor, enalaprilat. Moreover, it has been recently reported that G_<beta> stimulates PLA_2 in rat heart. In conclusion, elevated levels of endogenous angiotensin II induced after ingestion of a high protein diet may activate glomerular G_<beta>. Changes in renal hemodynamics observed in high protein intake may be caused by the action of vasodilatory eicosanoids, PGE_2 and 6-keto PGF_<1alpha>, which are augmented via the activated G_<beta>-induced increases in the activities of PE-specific-PLA_2 and cyclooxygenase.

高蛋白质摄入增加肾小球滤过率（GFR）和肾血浆流量。为了阐明其分子机制，我们检测了低蛋白（6%酪蛋白）或高蛋白（40%酪蛋白）饮食大鼠肾小球中类花生酸的产生、磷脂酰乙醇胺（PE）特异性磷脂酶A_2（PLA_2）和环氧合酶的活性以及G蛋白亚单位（G_<alphas>、G_<alphai2>、G_<alphai3>和G_<beta>）的含量。高蛋白组大鼠肾小球产生PGE_2、6-ketoPGF_2和TxB_2的量显著高于<1alpha>低蛋白组大鼠，且PE特异性PLA_2和环氧合酶活性显著升高。与低蛋白饮食大鼠相比，高蛋白饮食大鼠肾小球<alphai2>G_1和G_2降低，<alphai3>肾小球G_2升高<beta>。此外，通过用血管紧张素转换酶抑制剂依那普利拉预处理大鼠，在喂食高蛋白饮食的大鼠中观察到的这些变化也恢复到与在喂食低蛋白饮食的大鼠中观察到的水平相当。此外，最近有报道<beta>G_2刺激大鼠心脏PLA_2。结论：高蛋白饮食引起的内源性血管紧张素II水平升高可能激活肾小球G_2<beta>。高蛋白摄入引起的肾血流动力学改变可能是由于类花生酸、PGE_2和6-ketoPGF_2的扩血管作用，而<1alpha>G_2激活后引起的PE<beta>-特异性PLA_2和环氧合酶活性的增加又使其增强。

项目成果

H.Yanagisawa et al: "Protein increases glemerular eicesanoid production and activity of related eazymes" Kidney lnternational. 41. 1000-1007 (1992)

H.Yanagisawa 等人：“蛋白质增加肾小球类二十烷酸的产生和相关酶的活性”肾脏国际。

柳沢 裕之: "Medamism of emhanced eicosanoid gpdnctior by isolatel fomonli from rot and brtatenel uretenal obetmction" American Journal of Physiolagy. 261. F248-F255 (1991)

Hiroyuki Yanagisawa：“通过腐烂和 brtatenel uretenal obetmction 中的分离物增强类二十烷酸 gpdnctior”美国生理学杂志 261。F248-F255 (1991)

H.YANAGISAWA, et al.: "Protein increaces glomemlar eicosanoid production and activity of related engymes" Kidney clnternational. 41. 1000-1007 (1992)

H.YANAGISAWA 等人：“蛋白质增加肾小球类二十烷酸的产生和相关酶的活性”Kidney cinternational。

H.Yanagisawa et al: "Protein intake affects levels of G-protein subunits G_<αi2>,G_<αi>;and Gβ in rat glemerular membranes" Kidney lnternational.

H. Yanagisawa 等人：“蛋白质摄入量影响大鼠肾小球膜中 G 蛋白亚基 G_<αi2>、G_<αi> 和 Gβ 的水平”Kidney International。

H. Yanagisawa et al: "Protein increases glomeular eicosanoid production and activity of related enzynes" Kidney Int. 41. 1000-1007 (1992)

H. Yanagisawa 等人：“蛋白质可增加肾小球类二十烷酸的产生和相关酶的活性”Kidney Int。