Professor He Xuehong 's Academic Thought And The Clinical And Experimental Study On Treatment Of Chronic Kidney Disease With Renal Failure

Part one: Summary of Professor He Xuehong’s Academic Thought and Clinical Experience of Curing Chronic Kidney Disease with Shenshuaifang DecoctionPurpose: To organize and summarize professor He Xuehong’s academic thought and clinical experience.Details: 1.Professor He Xuehong’s academic thought mainly originated from the traditional Chinese medicine "four classic", Treatise on the spleen and stomach and Records of Tradition Chinese and Western Medicine in Combination. 2.Professor He Xuehong thought that the etiological factors of CKD mainly included congenital deficiency, the improper diet, etiology of work or rest, six-excess external contraction and oldness and weakness; in addition, there were also intensifying etiological factors such as phlegm, dampness, blood stasis and toxin due to the long process of disease. 3.Professor He Xuehong thought that CKD was a disease with deficient root including deficiency of spleen and kidney and excessive superficial including wet-stasis, which might generate a series of change causing by long-existing brewed toxin. 4.Professor He Xuehong creatively treated CKD as a kind of disease with Shaoyin organs’ yang deficiency generally and damp-heat retention locally according to the treatment thoughts of combination of exogenous febrile disease theory and epidemic febrile disease theory. 5.Professor He Xuehong created Shenshuaifang Decoction and therapeutic method based on syndrome differentiation to treat CKD3-4 according to the clinical characters of each stage of CKD and advantage of each school of traditional Chinese medicine.Part two: Retrospective analysis of 126 CKD3-4 spleen-kidney qi deficiency with blood stasis-damp turbidity cases integrated treated with Shenshuaifang decoction as principalPurpose:To retrospectively analyze the clinical effects of CKD3-4 spleen-kidney qi deficiency with blood stasis-damp turbidity cases integrated treated with Shenshuaifang decoction as principal.Material and method:168 cases diagnosed as CKD3-4 by western medicine and as spleen-kidney qi deficiency with blood stasis-damp turbidity by TCM who were hospitalized at the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine renal ward were divided into treatment group(126 cases) and control group(42 cases) according to whether having used Shenshuaifang decoction. The main symptoms, signs, renal function,serum electrolyte and other clinical data of both groups were collected and statistically analyzed by the electronic medical records system and Ruimei query system. Both disease and syndrome were evaluated and compared according to the diagnosis, symptoms-sign differentiation and curative effect evaluation of chronic renal failure.Results: 1.Treatment group made more obvious improvement on serum creatinine, e GFR and serum uric acid than control group. 2. In treatment group, more advanced stage subgroups made more obvious improvement on serum creatinine than the less ones. 3.In treatment group, there was not obvious difference of serum creatinine among all primary disease subgroups. 4.There was not obvious difference of serum electrolyte(eg.potassium, phosphorus, calcium) and carbon dioxide combining power between pretherapy and post-treatment.5.Treatment group had lower score of symptom than control group. 6.In treatment group, there was obvious difference of score of symptom among all disease-stage subgroups, and G4 subgroup made the most obvious improvement. 7.Treatment group had lower score of gastrointestinal symptom than control group. 8.Treatment group had higher effective rate of disease and syndrome than control group. 9.No significant adverse reactions was found in treatment group.Conclusion: 1.It could make CKD3-4 patients’ Scr and UA significantly reduced and e GFR effectively improved by Shenshuaifang decoction combined with routine treatment. 2.It made more ideal creatinine reduction effect in CKD4 stage than CKD3a-3b stage treated with Shenshuaifang decoction. 3.There was not relationship between curative effect of Shenshuaifang decoction and the primary disease leading to CKD. 4.Shenshuaifang decoction had no obvious significant effect on serum potassium, phosphorus, calcium and carbon dioxide combining power of CKD3-4 patients. 5.Shenshuaifang decoction could effectively relieve systemic symptoms in CKD3-4 patients, but there was not relationship between clinical efficacy and extent of disease. 6.Shenshuaifang decoction could effectively relieve gastrointestinal symptoms symptoms in CKD3-4 patients. 7.Shenshuaifang decoction could effectively improve clinical efficacy of disease and syndrome in CKD3-4 patients. 8.Shenshuaifang decoction within the application range of treatment had no significant adverse events.Part three: Experimental Research of the Mechanism of Shenshuaifang Decoction Remitting Adenine-induced Chronic Renal Failure Rats’ Renal FibrosisPurpose: To observe and analyze the mechanism of Shenshuaifang decoction remitting adenine-induced chronic renal failure Rats’ renal fibrosis by animal experiments.Material and method:46 SD rats as modeling group were prepared by Yokozawa model of chronic renal failure, while the remaining 10 rats as blank control group. After successful preparation of the model modeling group were randomly divided into high-dose group, conventional-dose group, losartan group and model group, which respectively were given by 20ml/kg Shenshuaifang decoction, 10ml/kg Shenshuaifang decoction, 10ml/kg losartan suspension and 10ml/kg purified water per day, and blank control group were also given by 10ml/kg purified water per day. Dosing period lasted for 8 weeks, during which period we recorded the rats’ body weight, active status and appearance. After dosing period we collected abdominal aortic blood for blood to check serum creatinine, blood urea nitrogen, alanine aminotransferase, TGF-β1 and MPC-1, weighted double kidney quality, collected left kidney tissue for biopsy, testing renal tissue TGF-β1、Smad2、Smad3 m RNA expression level by general-PCR, testing renal tissue MMP-1、MMP-9 and TIMP-1 m RNA expression level by fluorescence quantitative PCR and semi-quantitative analyzing renal tissue ColⅢ、ColⅣ expression level by mmunohistochemistry method. Then we statistically analyzed the result of the various results.Results: 1.During molding period modeling group rats’ weight gain rate was slower than blank group. During dosing period model group rats’ weight gained slower than any other group. Since the 6th week losartan group rats’ weight gained slow down, statistically different from the other group. high-dose group and conventional-dose group rats’ weight gained slightly more than losartan groupand model group, while there was no difference between high-dose group and conventional-dose group. 2. Renal index of model group was obviously higher than that of the other groups. Renal indexes of high-dose group, conventional-dose group and losartan group were all higher than that of blank group, but there was no difference among the three. 3.Blank group was not found obvious pathological change, and model group found the most obvious pathological change, followed by losartan group, high-dose group and conventional-dose group, but no obvious difference found between the latter two. 4.Serum creatinine level of high-dose group was obviously lower than conventional-dose group, losartan group and model group, but no difference found between the latter two. Blood urea nitrogen levels of high-dose group, conventional-dose group and losartan group were all lower than model group, but no difference found between the first three. There was no difference found in all groups’ alanine aminotransferase levels. 5.Serum TGF-β1 and MCP-1 levels of high-dose group, conventional-dose group and losartan group were all obviously lower than those of model group. The two results of high-dose group were not respectively different from those of conventional-dose group and blank group, but statistically different from those of losartan group. 6.Renal tissue TGF-β1, Smad2 and Smad3 m RNA expression levels respectively increased in turn in high-dose group, conventional-dose group, losartan group and model group. There was no statistical discrepancy of the three results between high-dose group and blank group, conventional-dose group and losartan group, while other groups were different from one another. 7.Renal tissue MMP-1、MMP-9 m RNA expression levels respectively decreased in turn in high-dose group, conventional-dose group, losartan group and model group. There was no statistical discrepancy of the two results between conventional-dose group and losartan group, while other groups were differentfrom one another. It shew the opposite tendency for TIMP-1 m RNA expression level. 8.Renal tissue ColⅢ、Ⅳ integral optical density respectively increased in turn in high-dose group, conventional-dose group, losartan group and model group. In ColⅢ expression there was no statistical discrepancy of the two results between high-dose group and blank group, conventional-dose group and losartan group, conventional-dose group and blank group, losartan group and model group, while other groups were different from one another. In ColⅣ expression there was no statistical discrepancy of the two results among high-dose group, conventional-dose group and losartan group, and blank group was respectively similar with high-dose group and conventional-dose group, while other groups were different from one another.Conclusion: 1. Adenine 200mg/kg gavage once per day could successfully build rat model of chronic renal failure, whose behavior and appearance characteristic, weight, renal function and renal pathological changes were all in line with ones of chronic renal failure. 2. Shenshuaifang decoction and losartan could both effectively increase body weight in rats with chronic renal failure and reduce renal index. 3. Shenshuaifang decoction and losartan could both relieve chronic renal failure rat kidney atrophy. 4.Shenshuaifang decoction and losartan could effectively relieve excessive deposition of extracellular matrix such as ColⅢ and ColⅣ excessive deposition to improve renal function though regulating serum MCP-1 levels, TGF-β1/Smad pathway and MMPs/TIMPs pathway. 5.Conventional dose Shenshuaifang decoctionand and losartan(rat 9mg/kg) received similar effects on various aspects just mentioned. 6.Double dose of Shenshuaifang decoction had more obvious advantages on alleviating renal fibrosis and protecting renal function than conventional dose of Shenshuaifang decoction and losartan(rat 9mg/kg). 7.Losartan, conventional and double dose of Shenshuaifang decoction had no hepatotoxicity.