The Relationship Between Inflammation And Diabetic Nephropathy Is Explored Based On The Theory Of Kidney Collateral Syndrome

Diabetic nephropathy(DN)as a common microvascular complications of diabetes,is the main reason of end-stage renal damage(ESRD).In recent years,the incidence of DN increased worldwide year by year.DN make a serious deterioration in the prognosis of diabetes,which increase the patients' medical costs largely.At present,the all treatment of DN can not prevent disease progression.So further research on pathogenesis of DN to find new therapeutic strategies can not only improve survial but also bring a huge economic and social benefits.DN has a complex pathogenesis,including glucose and lipid metabolic disorder,renal hemodynamic changes,oxidative stress,various cytokines,genetie factor and so on.The recenet study found that the pathogenesis has a close relationship with inflammation and some immunosuppressant can protect the kidney through its anti-inflammatory effects,which distinguish from the traditional therapeutic through improving metabolic and hemodynamic.But the study only stay in period of animal experiment.lt is still not clear that basic and clinical research about the treatment of chronic inflamnation to improve the prognosis of DN.DN is a kind of natural ilmune and low-level inflammation disease.Inflammation plays an important role in the progression of DN.The imbalance of Pro-inflammatory cytokines and anti-inflaumatory cytokine decides renal disease outcome.The pro-inflammatory cytokines IL-6 and TNF-? are close to the DN occurrence and can predict progression in advance.The IL-10 having anti-inflaumatory and immunosuppressive effects,is also close to the DN occurrence,while its mechanism is still controversial.The manifestations of DN are complicated,which often co-exist by virtual standard empirical,and change with the development of disease.There is almost no reports about the correlation between inflammatory factors and syndromes of DN.So investigating the correlation and giving the syndromes modem biology meaning have practical significance.Renal pathology make up for the deficiency of traditional Chinese medicine inspection.My tutor Professor Wang Yaoxian combined traditional Chinese medicine overall dialectical with renal microscopic pathology,enriched and developed the DN "micro zhengjia"doctrine to "Shenluozhengjia" theoretical system,raised the core pathogenesis being imbalance of "Shenluo Jusanxiaozhang",carried out experimental and clinical studies for the treatment of DN in traditional Chinese medicine guiding by "Shenluozhengjia",theoretical,and at the same time achieved great effect.lt may become a new method to explore the intervention of Chinese medicine to inflammation in the pathogenesis of DN.Objective:1.Base on Jusanshiheng pathogenesis,to explore the correlation between inflammatory cytokines and traditional Chinese medicine symptoms of DN.2.Using a rat model of type 2 diabetes nephropathy,to observe the shenyanfangshuaiye formula influence to the TNF-?/NF-KB inflammatory signaling pathways,oxidative stress and extracellular matrix accumulation;to study shenyanfangshuaiye formula interventional effect to inflammatory mechanisms in DN.Methods:1.Collect the Chinese medicine syndrome information of diabetic,diabetic nephropathy ?(DN ?),early diabetic nephropathy ?(DN ?,normal serum creatinine);reserve serum specimens;analyze the relationship between pro-inflammatory cytokines IL-6,TNF-? and biaoshi,the anti-inflammatory cytokine IL-10 and Benxu as well as the IL6/IL10 ratio change and imbalance of Jusanxiaozhang pathogenesis.2.The model of type 2 diabetic rats was established by uninephrectomy,fat diet feeding and STZ intraperitoneal injection.Experimental rats were divided into four groups:control group,model control group,Shenyanfangshuaiye formula group and irbesartan group.After eight weeks of administrating into a mold,rat weight,blood glucose,24h proteinuria,kidney/body weight ratio,serum total protein,albumin,total cholesterol,triglycerides,serum creatinine,blood urea nitrogen,glycol serum(MDA)and superoxide dismutase(SOD)were detected;renal pathological change was observed by HE and PAS;renal tissue TNF-?,NF-?bp65,TGF-?1 and Col ? protein were detected by immunohistochemical method;The expression of kidney tissue NADPHp22phox,TNF-?,NF-?bp65 and TGF-?1mRNA was detected by real-time fluorescent quantitative PCR.Results:Clinical research:1.The inflammatory cytokines IL-6 and TNF-? increase in early-stage DN(P<0.05 compared with the normal group),which act as a maker of early-stage renal damage.2.Shire syndrome is the main Biaoshi symptom in early-stage DN(34.07%).The pro-inflammatory cytokines IL-6 and TNF-? have a high expression in Shire,Tanzhuo and Xueyu syndrome(P<0.05 compared with the Qizhi syndrome);Qiyinliangxu syndrome is the main Benxu symptom(45.88%).The anti-inflammatory cytokines IL-10 decrease gradually with the progression of DN(P<0.05).3.The increase of IL-6/IL-10 ratio reflect the imbalance of the pro-inflammatory cytokines and anti-inflammatory cytokines.Meanwhile,the ratio increase with the progression of DN(P<0.05).Experimental research:1.Shenyanfangshuaiye formula can lower cholesterol levels(P<0.05),reduce albuminuria excretion(P<0.01),relieve renal pathological damage in model group(P<0.01).2.Shenyanfangshuaiye formula can reduce serum MDA production(P<0.01),increase SOD levels(P<0.01)and reduce the expression of kidney p22phoxmRNA in model group(P<0.05),thereby reduce oxidative stress and increase antioxidant capacity.3.Shenyanfangshuaiye formula can suppress the expression of TNF-? and NF-?Bp65 in model group(P<0.05),thus relieve the inflammation of kidney.4.Shenyanfangshuaiye formula can reduce the expression of TGF-?1(P<0.05),inhibit the produce of Col? in model group(P<0.05),so as to relieve the accumulation of ECM.Conclusion:(1)There is a high expression of inflammatory cytokines IL-6?TNF-? in early-stage DN;The pro-inflammatory cytokines IL-6 and TNF-? have a high expression in Shire,Tanzhuo and Xueyu syndrome;The increase of IL-6/IL-10 ratio reflect the imbalance of the pro-inflammatory cytokines and anti-inflammatory cytokines,which is the microscopic response of Jusanshiheng theory;The increase of IL-6/IL-10 ratio could predict the progression of DN.(2)Shenyanfangshuaiye formula can lower cholesterol levels,reduce albuminuria excretion,relieve renal pathological damage.The mechanism maybe related to restrain TNF-?/NF-?B inflammation signaling pathways,change the state of oxidative stress and reduce the expression of inflammatory cytokines.lt follows that inflammation is the main pathogenesis of DN and the ShenluoZhengjia theory has a guiding significance to the treatment of DN.