| The renal fibrosis is the common pathological character of most renal diseases. The animal model of Adriamycin-induced kidney fiborsis have the feature of the clinic progressive kidney injure, and it is similar to the human kidney disease. The Panax notoginseng saponins are the active components of the notoginseng which is belongs to the division of Acanthopanax gracilistylus and the Panax. The content of saponin in the root tuber is about 12%. The Rb1 and Rg1 is the major component which is same to the ginseng, and more than it contains. The pharmacologic action of notoginseng is that it can expand the blood vessel, inhibit platelet agglutination, prolong coag time, low blood-fat, clean free radical, anti-inflammatory, antioxygen, and so on. According to the theory of differentiation of symptoms and signs of TCM, the disease of desmoplasia is correlates to the syndrome of blood stasis, and the drug for invigorating blood circulation have an peculiarity efficiency on it. The marvelous effect of notoginseng is very relevancy to the therapeutic principles of eliminating pathogen to support vital qi on the organ fibrosis. Connective tissue growth factor is one of the downstream factors of TGF-β, and plays a very important part during the kidney fibrosis. Therefore, to study and research the effect of PNS on the abnormal expression of CTGF is significant to explain the mechanism of action on the adriamycin-induced nephropathy.ObjectiveTo observe the physiology and biochemical indicators, the major pathological and the expression of CTGFmRNA and It's protein in kidney tissue of the Adriamycin-induced Nephropathicy. To detect the GMCs proliferation after stimulate by the LPS, and the expression of CTGFmRNA and It's protein in their intracytoplasm, and the intervention of those index. To investigate the mechanism of action of Panax notoginseng saponins from the levels of unitary, tissue, cellule, protein, and gene, in order to provide the experimental basis on prevention and cure on kidney fibrosis of it.MethodsOne side nephrectomizes and ADR injection was used in vivo experiments, and the rats were divided into 5 groups: control group, sham operated group, model group, Benazepril group, PNS group. Each group has 10 rats. Benazepril is the positive medicine control groups. The following indexes were detected.1. The weight was measured each week,the Urine protein were measured every two weeks. BUN, Scr, Cho, TG, TP, Alb was measured before the rats were killed. The HE, PASM, Mallory and Masson dyeing was used to observe the pathomorphological changes of the rats kidney.2. The in situ hybridization was used to detect the expression of CTGFmRNA.3. The immunohistochemical method was used to detect the expression of CTGF protein.In the vitro experiments, study of intervention of PNS on the effect of GMCs stimulated by LPS. The cells were divided into control group, LPS group, Benazepril group, and PNS group.1. The human mesangial cells were cultured successfully in vitro. LPS was used to induce proliferation of mesangial cells. Changes of mesangial cell proliferation were detected by MTT reduction assay at 12 hours, 24 hours, 48 hours and 60 hours.2. RT-PCR was used to detecting the expression of CTGFmRNA in the intracytoplasm of GMCs stimulated by LPS.3. Immune immunohistochemical method and western-blot was used to detecting the expression of CTGF protein in the intracytoplasm of GMCs stimulated by LPS.Results1. In PNS group, the weight of rats were improved (comparing with model group P<0.05 or P<0.01), and the Urine protein was decreased significantly (comparing with model group P<0.05). The PNS can also reduce the BUN, Scr, Cho and TG (comparing with model group P<0.05), increase the TP and Alb (comparing with model group P<0.05), accordingly, it can improve the renal function, to correct the lipid-metabolic disorder, and relieve the pathology injury.2. PNS and Benazepril showed significant inhibitory function on the proliferation of mesangial cells (comparing with model group P<0.05), and there was no significant difference between the two groups.3. In PNS group, the expression of CTGFmRNA (comparing with model group P<0.05) was decreased, and the expression of CTGF protein was also significantly decreased (comparing with model group P<0.01). There was no significant difference between Panax notoginseng treatment group and Lotensin treatment group.4. Over expression of CTGFmRNA was controlled in PNS group and Benazepril group (comparing with LPS group P<0.01).5. In PNS and Rg1, Rb1 group, the expression of CTGF protein was significantly controlled (comparing with LPS group P<0.05).Conclusions1. PNS can correct the lipid-metabolic disorder, improve the renal function, reduced the urine protein excretion, and relieve the pathology injury.2. PNS can reduce proliferation of GMCs, and decrease the over expression of CTGFmRNA and It's protein in both inherent cells in renal and the GMCs in vitro, It's major components, Rb1 and Rg1 can reduce the expression of CTGF protein in the GMCs in vitro, and these maybe the mechanisms of PNS on retarding the renal fibrosis. |
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