| Objective:Through the collation of the origin and development of Bi disease theory in Huangdi Neijing and the literature of previous dynasties,This paper discusses the etiology,pathogenesis,syndrome and treatment of gouty arthritis combined with gouty nephropathy from the perspective of the theory of Bi disease in Neijing;according to the evolution characteristics of gout in western medicine,explores the correlation between the occurrence and transmission of five body Bi and five viscera Bi in Neijing,establishes the pathogenesis,syndrome and treatment of gouty nephropathy,and explores the effectiveness of Lingze mixture in the prevention and treatment of gouty nephropathy Theoretical basis.Secondly,animal experiments were carried out to observe the improvement of Lingze mixture on renal damage indexes such as urinary protein,blood uric acid,creatinine,urea nitrogen,Cystatin C,? 2-microglobulin and urokinase in rats with gouty nephropathy,observe the change of the appearance and morphology of the kidney in rats and measure the renal coefficient,and at the same time,to detect the effect of Lingze mixture on ABCG2 and Glu in rats with gouty nephropathy The effect of T9 and URAT1 on the level of expression,and then to explore the mechanism of Lingze mixture in the prevention and treatment of gouty nephropathy.The purpose of this study is to provide a full and detailed theoretical basis of traditional Chinese medicine for the clinical diagnosis and treatment of gouty nephropathy,guide the clinical practice,and promote the health of all human beings through the theoretical research and animal experimental research of literature.Research methods and contents:1.Theoretical research:1.1methods: Based on the theoretical research and the research methods of philology and Philology,through collecting and sorting out the relevant materials of Bi disease in the literature of the past dynasties,systematically sorting out the relevant treatises of Bi disease theory in Huangdi Neijing;Combing the literature about the correlation between "gout" and "Bi disease" in traditional Chinese medicine,discussing the five body Bi,five internal organs Bi and their interrelations in the theoretical system of Bi disease;elaborating the correlation of symptoms,etiology,pathogenesis,diagnosis and treatment of "gout",five internal organs Bi and gouty joint combined with gouty nephropathy from the theoretical system of Bi disease,exploring the prevention and treatment of gouty arthritis by traditional Chinese Medicine The effective treatment principles and prescriptions of kidney disease provide valuable theoretical basis for better clinical syndrome differentiation.1.2 results:(1)Neijing has built a relatively systematic and complete theoretical system of Bi disease,which is the theoretical source of the cause,mechanism,syndrome and treatment of Bi disease and gout in traditional Chinese medicine;(2)gout in traditional Chinese medicine belongs to the special type of Bi disease,which has the characteristics of pain in limbs and joints,acuteness of pain and repeated attacks,showing many similarities of gouty arthritis in modern medicine,which can be integrated with each other(3)gouty arthritis is equivalent to arthralgia of limbs,which is mainly composed of tendons and bones,foot and elbow joints.The development of the disease affects the liver,spleen,kidney and other organs,which belongs to five viscera arthralgia,especially closely related to kidney arthralgia.(4)The basic pathogenesis of gouty nephropathy is the deficiency of spleen and kidney,the combination of dampness,heat and blood stasis.2.Experimental research2.1 methods:A total of 100 male SPF SD rats were fed for 1 weeks.They were randomly divided into normal control group(normal group),10 rats and model group,Benzbromarone Tablets group(Western medicine positive control),Goufeng Ding capsule group(Chinese medicine positive control drug)and Ling Ze mixture low,medium and high dose group,and it is 15 rats in each group.The normal control group was given distilled water of equal volume.The remaining rats were given 15 g /(kg · d)by gavage every day for 1-4 days Yeast,5-22 days,was given 15 g /(kg · d)yeast + 100 mg /(kg · d)combined gavage for 22 days.On the 7th day of model making,66.6g / kg,33.3g / kg,16.65 g / kg,10 mg / kg and 0.86g/kg of Tongfengding capsule were administrated by gavage at the same time,and 20 ml / kg was administrated by gavage once a day for 28 days.On the28 th day after administration,the urine of each group was collected for 24 hours,the urine volume was measured for 24 hours,and the urine protein level,serum uric acid,creatinine and urea nitrogen,?2-microglobulin,urokinase,Cys C,Nag,URAT1,ABCG2 and GLu T9 were measured.At the same time,the changes of renal histomorphology were observed2.2 results:(1)The kidney of the normal control group was light brown,and the blood was well filled.The boundary of cortex and medulla was clear.In the model group,the volume of the kidney was significantly increased,and opalescent granules were seen on the surface of the kidney,which were densely distributed;the cortex was thinner,the elasticity was worse,the color was gray,and the change was obvious;the cut cortex and medulla were congested and edematous,and the junction of the cortex and medulla was abnormal and clear.Compared with the model group,the changes of kidney in each treatment group were slightly improved,and the number of kidney surface and milk self color granules was less than that in the model group.The number of milky granules on the kidney surface of each treatment group was less than that of the model group,and the therapeutic effect of high dose group of Lingze mixture was better than that of low dose group of Lingze mixture.(2)The experimental results show that Lingze mixture can affect URAT1,GLUT9 and ABCG2 in kidney It can be concluded that Lingze mixture can effectively prevent and treat gouty nephropathy by regulating the expression of several protein levels of urate transporter,thus reducing the reabsorption of uric acid by renal tubules,promoting the secretion of uric acid,increasing the excretion of uric acid,reducing the level of blood uric acid,and protecting the kidney and preventing and treating diseases.(3)the 24-hour urine volume and urine protein of the model group were significantly higher than that of the blank group(P < 0.001).Compared with the model group,the urine volume and protein content of each dose group of Lingze mixture,the group of benbromarone tablet and the group of Tongfengding capsule in 24 hours decreased significantly(P < 0.05,P < 0.01 or P < 0.001)(4)Compared with the blank group,the uric acid,creatinine and urea nitrogen in the model group increased significantly(P < 0.01).Compared with the model group,Lingze mixture high dose group and benbromarone tablet group can reduce the uric acid content of the model rats,with statistical significance(P < 0.05);Lingze mixture each dose group can reduce the serum creatinine level of the model rats,with significant difference(P < 0.01 or P < 0.001);Lingze mixture high dose group,benbromarone tablet group and Tongfengding capsule can reduce the urea nitrogen content There was significant difference(P < 0.05 or P < 0.01)(5)Compared with the blank group,?2-microglobulin,Cys C and NAG in the model group were significantly higher,while urokinase was significantly lower(P <0.01).Compared with the model group,each dose group of Lingze mixture and benbromarone tablet group can increase the content of urokinase and reduce the content of nag,which is statistically significant(P < 0.01);the high dose group of Lingze mixture,Tongfengding capsule group and benbromarone tablet group can reduce the Cys C expression was statistically significant(P < 0.05 or P < 0.01);the expression of ?2-microglobulin decreased in each dose group of Lingze mixture,Tongfengding capsule and benbromarone tablet group(P < 0.01 or P < 0.001).(6)Compared with the blank group,the average optical density of ABCG2 positive cells and GLu T9 positive cells in the model group decreased significantly(P< 0.01).Compared with the blank group,the expression of ABCG2 decreased,the expression of GLu T9 and URAT1 increased in the model group;compared with the model group,Lingze mixture can increase the expression of ABCG2,reduce the content of GLu T9 and URAT1,which is statistically significant.Conclusion:1.Huangdi Neijing has formed a relatively systematic and complete theoretical system of Bi disease,which is the theoretical base of the cause,mechanism,syndrome and treatment of Bi disease and gout in traditional Chinese medicine.2.Modern Gout belongs to the special type of Bi disease in traditional Chinese medicine.It has many similarities with gouty arthritis in modern medicine.It can be used for reference in etiology,pathology,diagnosis and treatment;3.According to the theory and research of Bi disease in Neijing,it is found that gouty arthritis is equivalent to bi disease in limbs,mainly in muscles and elbows,which can be attributed to five body Bi;when the disease can affect the liver,spleen,kidney and other organs,it can be attributed to five viscera Bi,especially closely related to kidney Bi.Gouty arthritis evolves to gouty nephropathy with the development of the disease,which is consistent with the law of development and evolution of five body arthralgia(limb arthralgia)and five internal organs arthralgia in traditional Chinese medicine.4.The basic pathogenesis of gouty nephropathy is the deficiency of spleen and kidney,the disadvantageous gasification,and the accumulation of dampness,heat,turbidity and blood stasis.Because of the weakness of temper and the weakness of transport and transformation,the Yang will not rise.It is easy to generate dampness and evil and block the Qi mechanism,and there will be the change of phlegm and blood stasis and fire.The accumulation of dampness,heat,turbidity and blood stasis,blocking the three jiao,hindering the Qi mechanism,causing the Qing Yang not to rise but to sink,the turbid Yin not to fall but to go up,the Qi mechanism to rise and fall maladjusted,and the ascending and descending reverse order.Dampness,heat,turbidity,blood stasis,toxin and other pathogenic factors are not only pathological products but also pathogenic factors,which further hinder the operation of Qi mechanism of Sanjiao,affect the functional activities of liver,spleen,kidney and other viscera,and further promote the lingering and refractory diseases.The dampness is sticky,the dampness evil is easy to form phlegm and blood stasis,and heat and fire are turned into poison.The treatment should be based on promoting dampness and turbidness,strengthening the spleen and benefiting Qi as the first opportunity,which can not only replenish the middle Qi,but also consolidate the lower elements,so as to achieve the same treatment of Tonifying the spleen and benefiting the kidney.5.According to the etiology and pathogenesis of gouty nephropathy,the "Lingze mixture" is proposed to prevent and treat gouty nephropathy.Lingze mixture is mainly composed of Smilax,Alisma orientalis,Atractylodes macrocephala,phellodendron,astragalus,angelica,white peony,safflower,etc.it has the function of "clearing away heat and turbidity,relieving dampness and pain,activating blood and dredging collaterals,and tonifying the spleen and kidney".It can achieve the goal of curing joints and improving kidney damage.6.The experimental results of Lingze mixture on rats with gouty nephropathy showed that Lingze mixture could improve the renal tissue morphology,significantly reduce the kidney coefficient,SCR,bun,24 h albuminuria,Cystatin C,urinary n-acetyl-?-d-glucosidase(NAG)and ? 2-microglobulin,improve the renal damage,increase the level of urokinase and prevent the renal damage In addition,Lingze mixture can regulate the protein expression of urate transporters such as URAT1,GLUT9 and ABCG2 in the kidney of the model rats,reduce the reabsorption of uric acid by renal tubules,increase its excretion of uric acid,reduce the level of blood uric acid,and achieve the purpose and effect of prevention and treatment of gouty nephropathy.7.This study proved that Linze mixture can reduce blood uric acid,improve renal function and prevent renal fibrosis from both theoretical and experimental aspects.It also provides effective prescription and sufficient theoretical basis for clinical prevention and treatment of gouty nephropathy.8.According to the theory of pathogenesis and syndrome treatment of Bi disease in Neijing,effective intervention and prevention of traditional Chinese medicine in the early stage of Bi disease can achieve satisfactory and effective treatment effect,reduce the patients' pain,protect human health and benefit the society. |
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