The Investigation Of The Level Of Plasma Lysophosphatidic Acid And Expression Of Its Membrane Receptor Edg-7 In 5/6 Nephrectomy Rats And Renal Protection Of Abelmoschus Manihot

Chronic renal failure is the result caused by renal chronic lesion originated by kinds of reasons and progressing aggravation. Renal interstitium fibrosis is the main patho-change and common route from various of renal diseases to renal failure. More and more evidence prove that the metabolic disorder of fatty substance is the chief factor of the fibrosis's progression. As a representation of metabolic disorder of fatty substance, phosphatide disorder has been attracting more scholars'attentions. Lysophosphatidic acid is the simplest phosphatide. It's the production of membrane phospholipids metabolism and a important member of phosphatide grows factors which play a wider biological effect. From aspect of renal, lysophosphatidic acid can accelerate the cell proliferation; derivate the renal mesangial cells and collagenoblast cells express growth factor of connective tissue; accelerate the proliferation of renal tubular epithelial cells and resist the apoptosis. As we know, the LPA1 LPA2 and LPA3 are members of family of endothelial tissue differentiation and growth acceptor. LPA3 (Edg-7) is the most expression in range of renal and corpus glandulare prostatae. LPA educes its biological function by coupling Gi proteinum to activiate related signal iter (for instance, Ras-MARK iter) after conjunction with its receptor. Edg-7 is able to facilitate the proliferation of mesangial cells after conjunction with LPA, blocking EDG-7's action will cause a result that the proliferation of mesangial cells mediated by LPA is also blocked. TGF-β1 is a kind of multifunctional cytokine which regulates profileration, differentiation and apoptosis with the complex receptor signals conduction on the cell surface by the means of autocrine, paracrine and endocrine.Activated TGF-β1 can produce renal fibrosis related reactions, including increase of interstitial substance's production,restraint of interstitial substance's degradation and chemotaxis of desmocytes and monocytes.Pharmacology study has suggested that the Abelmoschus manihot (L) medic has the effects of anti-imflammation, antilipemic, eliminating the oxygen free radical, etc. A main component of it-Quercetin, can inhibited the growth of mesangial cells and reduce accumulation of extracellular matrix. The objective of our study is to discuss the protection of Abelmoschus manihot (L) medic to 30 chronic renal failure patients and rats with 5/6 nephrectomy and the action mechanism of anti-fibrosis.This experiment divides to two parts contains clinical observation and foundation research ,plans to view the protection of Abelmoschus manihot (L) medic to CRF patiens and renal interstitium fibrosis-rats with 5/6 nephrectomy and research the effective of plasm LPA and genetic expression of membrane receptor Edg-7. To select 30 CRF patients ,rats set up sham operation group,model group and Abelmosehus moschatus group,determine each group plasma LPA level,and determine the effect that Abelmosehus moschatus has on serum TGF-β1 level and Edg-7mRNA's expression with the methods of ELASA,RT-PCR. Follow is the conclusion: 1. LPA,TGF-β1 has a obvious increase while group of the rats with 5/6 nephrectomy. This conclusion shows that LPA can accelerate the proliferation of the glomerular mesangial cells and cause the interstitial fibrosis. 2. LPA's membrane receptor Edg-7 can conjugate with LPA to accelebrate the proliferation of the mesangial cells through activating the Ras-MARK。Down-regulating the mRNA expression of Edg-7 may be an effective method of blocking the proliferation of the mesangial cells. 3. Abelmosehus moschatus can down-regulate the mRNA expression of Edg-7 of the rats with 5/6 nephrectomy. It can also decrease the level of TGF-β1 and mitigate the fibrotic grade. 4. Abelmoschus manihot(L.)medic can inhibit the proliferation of the mesangial cells and may relate with down-regulation of the mRNA expression of Edg-7.