摘要
为明确黄芪、当归在肾病综合征 (nephroticsyndrome ,NS)治疗中的作用、适应证及其作用机制 ,我们从临床和实验两方面进行了系统的研究。 (1)黄芪当归合剂对肾脏的保护作用 :各种肾脏疾病慢性病变经过肾硬化、纤维化 ,最终发展成为终末期肾衰竭。如何阻断这一发展通路已成为国际肾脏病界研究的热点。本研究选用慢性嘌呤霉素肾病模型 ,以目前公认具有肾脏保护作用的血管紧张素转化酶抑制剂 (ACEI)作为阳性对照 ,经 12周给药观察后处死 ,收集血、尿、肾脏标本进行检测。结果显示模型鼠肾脏呈慢性炎症 ,肾小球硬化和小管间质纤维化。黄芪当归合剂 (A&A)治疗明显减轻肾功能恶化和组织学损伤 ,肾小球硬化指数和小管间质损伤指数下降与肾功能损伤减轻呈正相关 (r=0 .80 ,P <0 .0 0 1和r=0 .85 ,P <0 .0 0 1)。细胞外基质Ⅲ、Ⅳ型胶原 ,纤连蛋白和层粘连蛋白明显减少。这种抗纤维化作用与ACEI相似 ,但肾局部的血管紧张素Ⅱ水平不下降 (5 6 .5 3± 7.0 3vs 76 .6 2± 12 .88pg/mg蛋白 ,P <0 .0 5 )。然而 ,A&A治疗组的肾脏转化生长因子 β1(TGF β1) (0 .0 5 17± 0 .0 2 4 8vs 0 .110 0± 0 .0 2 6 1,P <0 .0 5 )和骨桥蛋白 (OPN ,0 .0 10 5± 0 .0 0 5 3vs 0 .115± 0 .0 34,P <0 .0 5 )表达 ,单核
The mixture of two Chinese herbs, Astragalus an d Angelica (A&A), has been used f or the treatment of nephritic syndrome (NS) in China for years. The effectivenes s of these two herbs has been proved in traditional Chinese clinical practice. I n early 1950's, the effect of Astragalus and Angelica in treatment of NS had been evaluated in our department and got positive conclusion. Based on th is in vestigation, we systematically studied with both clinical and experimental metho ds, to elucidate the curative effect, mechanism and indication of the mixture of these two Chinese herbs. (1)Renoprotective effects of Astragalus and Angelica :progressive renal disease is a common result of diverse etiologies defined by th e fact that there are renal fibrosis and sclerosis, accompanied by a progressiv e decline in renal function despite the elimination or amelioration of the initi ating stimulus. How to block the pass way is a prime objective in clinical nephr ology.Chronic puromycin nephrosis rats were randomly divided into NS control ( n =7), A&A ( n =7) (3 ml·d -1 ) or ACEI ( n =7) (enalapril 10 mg·k g -1 ·d -1 ) treated groups. After 12 weeks, serum, urine and renal tissue were collected for study. In untreated rats, chronic renal injury progressed with marked fibrosis at the e nd of 12 we eks. A&A obviously ameliorated deterioration of renal function and improved hist ologic changes. The expression of type Ⅲ, Ⅳ collagen, fibronecti n and laminin was significantly decreased. This anti-fibrosis effect w as com parable to ACEI. In A&A group, the renal local angiotensin Ⅱ (Ang Ⅱ) level (56 .53±7.03) remained as high as in NS untreated rats (76.62±12.88), but rena l Ang Ⅱ level (34.36±4.89) and ACE activity were significantly decreased in AC EI group. However, in A&A treated rats, the overexpression of TGF-β 1 (0.051 7 ±0.024 8 vs 0.110 0±0.026 1, P <0.05) and OPN(0.010 5±0.005 3 vs 0.115±0.034 , P <0.05), ED-1 positive cells (12.8±10.9/HP vs 27.1±9.1/HP, P <0.05) and α-SMA positive (0.001 7 ± 0.000 53 vs 0.015 40±0.007 90, P < 0.01 ) were much less tha n in NS untreated rats.The A&A retarded the progression of renal fibrosis and renal function deteriorat i on,which is similar to the effect of ACEI. These renoprotective effects wer e not via inhibitory renal Ang Ⅱ, whereas they were associated with suppression of TG F-β 1 and OPN overexpression, reduction of both infiltration of monocyte/macr oph age and activation of renal intrinsic cells.(2)The effects of Astragalus and Angelica mixture on protein metabolism of nephritic syndrome:we found that A&A could ameliorate hypoalbuminemia in NS patients and animal mod els incongruity with the decreasing of urinary protein. In the following systemi c investigations A&A was demonstrated to increase the net rate of protein synthe sis in NS patients, which had been confirmed by protein turnover study with 15 N- Glycine. Northern blot and nuclear run on studies on hepatic cells of NS rats fu rther demonstrated A&A's effect on the up-regulation of albumin gene tran scription. The effect of A&A was better than any components of Astragalus or Angelica. (3)The effect of Astragalus and Angelica mixture on hyperlipidemia of ne phrotic syndrome:rats with nephrotic syndrome from accelerated nephrotoxic serum nephritis were u sed. The expression of two lipid metabolism related enzyme, 3-hydroxy -3-m ethyl gl utaryl-coA reductase (HMG-CoA-R), the rate-limiting e nzyme of cholesterol biosyn thesis and low-density lipoprotein receptor (LDL-R) were measured by Northern bl ot. The activities of two enzymes involved in lipoprotein clearance, lipoprotein lipase (LPL) and lecithin-cholesterol acyltransferase ( LCAT) were also tested b y biochemistry methods. In A&A treatment group, serum total cholesterol, triglyc eride, low-density and very low-density lipoproteins were significantly low th an those in nephritic control group. There was no change in the amoun
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2002年第5期542-552,共11页
Journal of Peking University:Health Sciences
基金
国家自然科学基金 ( 3 9670 90 9
3 9970 92 9)
卫生部科研基金 ( 94 1 2 76)资助
关键词
肾变病综合征
中医药疗法
黄芪
当归
药理学
Nephrotic syndrome/TCM ther
Astragalus membranaceus /ph armacol
Angelica sinensis /pharmacol
