LOX-1对食盐敏感性高血压大鼠肾损害进展的影响及中药干预作用

Effect of Baoshenpian Tablet on the Gene Expression of Oxidized Low-density Lipoprotein Receptor and Cytokines in Experimental Hypertensive Glomerulosclerosis

目的:围绕内皮氧化低密度脂蛋白受体(LOX-1)与高血压和肾损害的机制,从分子生物学方面探讨中药保肾片对LOX-1以及细胞增殖因子TGF-β、细胞外基质主要成分Ⅰ型胶原的影响。方法:对DS、DR系大鼠半数予以高食盐饮食,其余予对照饮食,另设高食盐饮食+中药保肾片高、低剂量2组。4周实验结束后断头处死,切取肾脏,测定有关生化指标,并提取总RNA,RT-PCR处理制备探针,Northernblot测定LOX-1、TGF-β、Ⅰ型胶原的mRNA表达。结果:(1)服用8%高食盐的DS大鼠主动脉及肾脏LOX-1mRNA表达显著上调。(2)高食盐DS大鼠LOX-1升高同时可见TGF-β和Ⅰ型胶原mRNA表达增加。(3)DS高食盐大鼠见到血压升高,血胆固醇、甘油三酯升高,血肌酐升高,尿蛋白排泄增多。(4)中药保肾片与对照组相比,DS8%高食盐大鼠的LOX-1、TGF-β、Ⅰ型胶原的mRNA表达显著降低,血压、血脂、血肌酐、尿蛋白亦见明显下降。结论:(1)LOX-1在高血压大鼠的主动脉上mRNA表达上调,可能与内皮依赖性血管舒张的损害有关。(2)食盐敏感性DS大鼠的高血压肾损害进展与LOX-1升高、多种细胞增殖因子及细胞外基质产生增加有关。(3)保肾片可显著降低LOX-1的mRNA表达及TGF-β、Ⅰ型胶原的产生,降低血压和蛋白尿,改善脂质水平和肾损害。中药保肾片治疗慢性肾衰竭、延缓高血压肾损害进展的作用机制与降低肾脏中LOX-1、TGF-β及Ⅰ型胶原的mRNA表达有关。

Objective To investigate the effect of the Chinese Herbal Medicine Baoshenpian tablet.on oxidized lowdensity lipoprotein receeptorl（LOX- 1）, transforming growth fator- β（TGF- β） ,type Ⅰ collagen（Col Ⅰ ）in Dalai salt - sensitive （DS） rats fed with high-salt （8% NaCl） diet and the moleculobiological mechanism of LOX- 1 in hypertension and renal damage. Methods：Two groups of rats were studied：DS rats and DR rats. Half of rats in each group were fed with high - salt diet, the rest were fed with low - salt diet. Another two groups of DS rats with high - salt diet were given high or low dose of Baoshenpian tablet. After 4 weeks of treatment, kidneys were excised for extraction of RNA and preparing of probe by reverse - transcription - PCR. The LOX - 1, TGF - β and Col Ⅰ mRNA expression was assessed by Northern blot analysis while some biochemical indices were observed. Results： LOX- 1 mRNA expression in the aorta was significantly elevated in hypertensive DS 8% rats. The upregulation of LOX- 1 in DS8% rats was accompanied by renal overexpression of TGF- β and Col Ⅰ , impaired renal function and elevated Bp and serum lipid , all of which were ameliorated by Baoshenpian tablet. Conclusion： （1）The upregulatiun of LOX- 1 in the aorta of hypertensive rats may be related to the lesion of endothelium-derived vasodiatory effects. （2）The renal overexpression of LOX- 1, growth factors and extracellular matrix proteins are responsible for renal damage in hypertensive rats. （3）Chinese Herbal Medicine Baoshenpian tablet can downregulate the gene expression of LOX- 1 ,TGF-β and Col and can decrease Bp,serum lipid, urinary protein excretion and serum creatinine. The therapeutic mechanism of Baoshenpian tablet in delaying the progress of hypertensive renal damage may be related to its downregulation of the expression of LOX - 1, TGF- β and Col I.