| Objective: (1)To review the research advancement on the pathogenesy and the therapy of prevention and cure in renal fiabrosis. (2)To observe the clinical efficacy on chronic renal failure(CRF) and the anti-renal fibrosis effect of Chinese traditional medicine Niaoduqing Capsules(NDQC) by the therapy of tonifying and lifting clear QI and excreting pathogenic QI. (3)To explore the mechanism of action of NDQJN on renal fibrosis.Methods:(1)Literature study:To look up a great deal of internal and foreign research documents about the pathogenesy and the therapy of prevention and cure in TCM and western medicine on renal fiabrosis, and summarize and assess these datas. (2)Clinical research:Seventy-eight patients with CRF were randomly and equally divided into subject group and control group .The subject group was administered by symptomatic treatment medicines and NDQC, and the control group was administered by symptomatic treatment medicines and Oxyamyli tectus Aldehydum(OTA). The cardinal symptoms and laboratory examination indexes were observed . The cardinal symptoms included bad appetite, abdominal distension, nausea and vomiting, lassitude, sore waist or knee, skin pruritus, pale face or lip and nails, squamous and dry skin, cold body and limbs, feverish palms and soles, edema, and dizziness. The laboratory examination items contained haematoglobin(HB), red blood cell number(RBC), serum creatinine(Scr), serum urea nitrogen(BUN), creatinine clearance(Ccr), seralbumin(ALB), total cholesterol(Teh), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), serum laminin(LN), precollagen-III(PC-III) , and hyaluronic acid (HA). These items was respectively determined before administration and after eight weeks. The number of patients with dialysis treatment, because of aggravated patient's condition, was recorded in follow-up four months. (3)Experimental study:Human renal tubular epithelial cells (HK-2) were respectively cultured in six different media. Theywere normal control group , 5% uremic serum group, 10% uremic serum group, 5% NDQC serum group, 10% NDQC serum group and Monopril geoup(fosinopril density was 10~6mmol/L). Cell proliferation was measured by methylene blue assay (MTT method). Cell life cycle and the positive cell percentage of a-smooth muscle actin(a-SMA) in every group were evaluated by flow cytometry. Connective tissue growth factor messenger RNA (CTGFmRNA) was detected by reverse transcript ion-polymerase chain reaction(RT-PCR) method.Results: (DReview of publications:There was no the nomenclature 'renal fibrosis' in TCM, but the clinical manifestation of renal fibrosis or CRF was discovered in these diseases such as 'edema' , 'frequent vomiting and dysuria' , 'anuria' , 'asthenia' , 'lumbago' and so on. The etiopathogenisis and pathogenesis of renal fibrosis was summarized as asthenia in origin and state of evil domination in superficiality. The asthenia was mainly due to the deficiency of spleen and kidney, and the state of evil domination mainly included stagnation of damp-heat in triple warmer , turbid toxin in body, obstruction of collaterals by blood stasis. The therapeutic methods of cleaning out FU-organ and excreting turbid pathogen were mainly taken , and tonifying QI and invigorating the kidney were also used at the same time in CRF. The materia medica for CRF contained compound preparation, single pharmaceutical product , and simple substance of effective ingredients extracted. Thier mechanisms of action on renal fibrosis were that they inhibited cell proliferation and transdifferentiation , restrained the production of fibrotic factors, and reduced the deposition of extracellular matrix (ECM) in kidney. TCM had satisfactory curative effect on renal fibrosis. At the viewpoint , the pathogenesy of renal fibrosis related to activation and proliferation of renal cells, infiltration of mononuclear macrophage, production and secretion of mediators of inflammation and cytokines. These resulted in destruction of normal kidney structure and deposition of ECM, and fibrous degeneration finally. Epithelium- mesenchymal transdifferentiation(EMT) was one of important pathogenesies in renal fibrosis. Transforming growth factor-P 1(TGF-0 1 ) and CTGF are important growth factor inducing renal fibrosis. People are researching new methods or medicines to prevent and cure renal fibrosis. They may inhibit cell proliferation and EMT , or prevent these cells from secreting or synthesizing cytokines that results in renal fibrosis. Cytokines antagon are also being studied. Some of these medicines have beenadministered in some patients, but their therapeutic effect are dissatisfactory. ?The clinical research:The total score of all symptoms and the single score of most of symptoms were both remarkable fewer in subject group than in control group (p<0. 05 UK p<0. 01) .The curative effect rate of symptom and total effective power were both more higher in subject group than in control group(p<0. 05 or p<0. 01) .The levels of ALB and HDL-C were more higher , and the levels of Tchu TG> BUN> Scr> Ccr> LI^ PC-IIL HA were much lower in subject group than in control group(p<0. 05 or p<0. 01) .NDQC remarkably decreased the number of patients who accepted dialytic medication in six months (p<0. 05). ?Experimental study: (DAbsorbance 490(A490) was remarkably higher in 5% uremic serum group and 10% uremic serum group than in normal control group with use of MTT(p<0.01) ,and that was without significant difference between 5% NDQC serum group and 5% uremic serum group (p>0. 05) , and that was much lower both in 10% NDQC serum group and in monopril group than in 5% uremic serum group (both p<0. 01) .No significant difference of A490 was found among 5% NDQC serum group, 10% NDQC serum group, monopril group and normal control group (p>0. 05) .?The percentage of cells in GO/G1 phase was remarkably lower in 5% uremic serum group and 10% uremic serum group than in normal control group with use of flow cytometry(p<0. 01), and that was without significant difference between 5% uremic serum group and 10% uremic serum group (p>0. 05) .It was increased significantly in 5% NDQC serum group, 10% NDQC serum group, and monopril group compared with that in 5% uremic serum group (all p<0.01) , and it was not showed significant difference among the fist three group (p>0. 05) .The percentage was lower significantly in 5% NDQC serum group than that in normal control group (p<0.05) ,but No significant difference of the percentage was found among 10% NDQC serum group, monopril group and normal control group (p>0.05) . ?Proliferation index(PI) of HK-2 was increased significantly in 5% uremic serum group , 10% uremic serum group and 5% NDQC serum group than that in normal control group with use of flow cytometry (p<0.01) ,but the PI was without significant difference among 10% NDQC serum group, monopril group and normal control group (p>0. 05) . It was decreased significantly in 5% NDQC serum group, 10% NDQC serum group, and monopril group compared with that in 5% uremic serum group (all p<0.01) .No significant difference of the PI was found among 5% NDQC serum group, 10% NDQC serum group, and monopril group (p>0. 05) . ?The positive percentage of a -SMAcells was increased significantly in 5% uremic serum group and 10% uremic serum group than that in normal control group with use of flow cytometry (p<0. 01) , but no significant difference between the first two groups (p>0. 05) .It wasn' t decreased significantly in 5% NDQC serum group compared with that in 5% uremic serum group (p>0. 05) , but it was significantly higher in this group than in normal control group (p<0. 01) . The positive percentage was remarkably lower in 10% NDQC serum group and monopril group than in 5% uremic serum group (both p<0. 01) , but higher than in normal control group (p<0. 05) . No significant difference of the positive percentage was found among 5% NDQC serum group, 10% NDQC serum group and monopril group (p>0. 05) . ?The expression of CTGFmRNA was much lower in normal control group than in others (all p<0. 01) , The expression in 10% uremic serum group was highest in all groups (p<0. 01) . No significant difference was found in 5% NDQC serum group compared with that in 5% uremic serum group (p>0. 05) . CTGFmRNA expression was remarkably lower in 10% NDQC serum group and monopril group than in 5% uremic serum group (both p<0.05) . No significant difference of CTGFmRNA expression was found among 5% NDQC serum group, 10% NDQC serum group and monopril group (p>0. 05) . Conclusion: (DThe pathogenesy of renal firosis in CRF is a complicated and interacting network mechanism. Many component elements in the mechanism are not distinct. Most of prevention and cure methods of renal firosis are still in research , and their therapeutic effects are yet dissatisfactory in clinic. TCM has manifested satisfactory anti-renal fibrosis effect and favourable clinical application perspective . (2) NDQC implied 'tonifying and lifting clear QI and excreting turbid pathogen' not only improved clinical symptoms , but also protected renal function, and decreased the fibrotic indexes in CRF patients.All these results show NDQC is a satisfactory inhibitor of renal fibrosis. (3)The mechanism of action of NDQC on renal fibrosis possibly relates to inhibiting cell proliferation and EMT, and preventing cells from synthetizing or secreting fibrotic cytokines. This research result will provide experimental evidence for NDQC s clinical application.
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