ROLE OF KLOTHO GENE IN RENAL PROTECTION

高盐(8%Nacl)饲料喂养的Dahl盐敏感型高血压(Dahl-S)大鼠肾脏Klotho mRNA的表达明显低于低盐(0.3%Nacl)饲料喂养的大鼠(n=7)。Klotho基因注射每周1次，连续3周，可诱导注射部位Klotho基因表达。氧化型荧光染料氢乙啶用于原位检测超氧化物歧化水平。肌注Klotho基因可减少主动脉超氧化物的生成，使内皮功能障碍从对照组的43±6%恢复到61±9%(n=6，p&lt；0.05)。同时，收缩压从262±11 mm Hg降至234±6 mm Hg(p&lt；0.05)。此外，Klotho基因转移将血管周围纤维化从0.031±0.002改善到0.011±0.001 mm^2，并将蛋白尿从2.5±0.4g/d减少到0.31±0.14g/d(n=8，p&lt；0.05)。我们的研究表明，Klotho基因肌肉注射减少了氧化应激，保护了达尔-S大鼠的血管内皮。我们认为，诱导Klotho基因的表达与改善内皮功能有关，可能是治疗高血压所致肾功能衰竭的一种潜在的新策略。

The expression of klotho mRNA in the kidney was significantly reduced in Dahl salt-sensitive hypertensive (Dahl-S) rats fed high salt (8% NaCl) diet as compared to those fed low salt (0.3% NaCl) diet (n=7). The klotho gene delivery once a week for 3 weeks induced klotho mRNA expression at the injection site. Hydroethidine, an oxidative fluorescent dye, was used to evaluate the levels of superoxide in situ. Intramuscular induction of the klotho gene decreased in superoxide production in the aorta, resulting in restoration of endothelial dysfunction from 43±6 % to 61±9 % of control rats (n=6, p<0.05). At the same time, systolic blood pressure was reduced from 262±11 mmHg to 234±6 mmHg (p<0.05). Furthermore, klotho gene delivery improved perivascular fibrosis from 0.031±0.002 to 0.011±0.001 mm^2 and reduced albuminuria from 2.5±0.4 to 0.31±0.14 g/day (n=8, p<0.05).Our study indicates that intramusclar delivery of the klotho gene reduces oxidative stress and protects the vascular endothelium in Dhal-S rats. We suggest that induction of the klotho gene expression associated with the improvement of the endothelial function may be a potential novel therapeutic strategy for renal failure induced by hypertension.