[Modulation of aberrant extracellular matrix degradation systems by astragali radix and angelicae sinensis radix decoction (A&A) in interstitial fibrotic kidney].
ABSTRACT The imbalance between extracellular matrix (ECM) synthesis and degradation induces the excessive ECM deposition and thus renal fibrosis. The decoction (A&A) which is a combination of two Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, has been shown to alleviate ECM production in animal models of chronic kidney diseases. In this paper, the effect of A&A on ECM degradation was investigated with interstitial fibrosis in rats.
Male Wistar rats were randomly divided into sham, unilateral ureteral obstruction (UUO) and UAA (UUO plus A&A administration) groups. After administration of A&A (14 g x kg(-1) x d(-1)) by gavage for 3, 7 and 10 days, morphological changes were evaluated by HE, PAS and Sirius red staining technique. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), the activity of PAI-1 and t-PA were determined by ELISA. The activity of matrix metalloproteinases (MMP-9, MMP-2), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were evaluated by gelatin zymography or reverse gelatin zymography, respectively.
Morphological analysis showed severe interstitial mononuclear cells infiltration, tubular atrophy, renal fibrosis and collagen expression in kidneys of UUO group, which was reduced by A&A administration (P < 0.05, UAA vs UUO group). Compared with the sham group, the expression of PAI-1 was significantly increased in UUO group by 63%, 91% and 112% at day 3, 7 and 10 respectively; and there were a remarkable decrease in UAA group by 44%, 43% and 52% at day 3, 7 and 10. The expression of active PAI-1 was strikingly increased in UUO group at day 3 [(30.5 +/- 23.8) ng x g(-1) vs. (0.0 +/- 0.0) ng x g(-1), P < 0.05)], day 7 [(36.5 +/- 11.2) ng x g(-1) vs. (0.0 +/- 0.0) ng x g(-1), P < 0.05)], and day 10 [(54.5 +/- 14.2) ng x g(-1) vs. (0.5 +/- 0.5) ng x g(-1), P < 0.05)]. The active PAI-1 was decreased in UAA group at day 7 [(14.9 +/- 0.5) ng x g(-1) vs. (36.5 +/- 11.2) ng x g(-1), P < 0.05] and day 10 [(15.4 +/- 4.8) ng x g(-1) vs. (54.5 +/- 14.2) ng x g(-1), P < 0.05]. The expression of t-PA was increased in UUO group only at day 3 [(58.1 +/- 16.5) microg x g(-1) vs. (30.1 +/- 17.3) microg x g(-1)], P < 0.05), meanwhile decreased in UAA group [(26.3 +/- 8.7) microg x g(-1) vs. (58.1 +/- 16.5) microg x g(-1), P < 0.05)]. But the expression of active t-PA was shown no significantly difference among the three groups. For MMP-2 and MMP-9 activity, they were significantly higher compared with the sham group in UUO group, but no significantly change after A&A treatment. The TIMP-1 activity was significantly increased in UUO group by 28% and 63% at day 7 and 10 respectively, significantly decreased in UAA group by 40% and 39% at the same time point.
The anti-fibrosis effects of A&A might be associated with modulating the imbalance of PAs/PAIs system as well as MMPs/TIMPs system, thereby alleviate ECM accumulation and interstitial fibrosis.
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ABSTRACT: Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.African Journal of Traditional, Complementary and Alternative Medicines 01/2014; 11(1):194-204. · 0.52 Impact Factor