| In recent years,with the changes in dietary structure of Chinese residents,the incidence rate of hyperuricemia is increasing annually and patients with hyperuricemia tend towards younger.Studies have shown that hyperuricemia is one of the independent risk factors for new-onset chronic kidney disease,which causes uric acid nephropathy(UAN).Early clinical symptoms of UAN are insidious,and easy to be misdiagnosed.The patients with UAN had different appearance such as proteinuria,hematuria,low back pain as the primary symptom,the renal function often decreased and progressed to chronic uric acid nephropathy(CUAN)at the time.CUAN is a disease cause great harm if not treated in time and can lead to end-stage renal failure,often complicated with cardiovascular diseases,nervous system diseases and other diseases.At present,the curative effect of Western medicine mainly containing lowering blood uric acid,protecting residual kidney function,preventing and treating complications for CUAN,but the uses of a large number of drugs cause a variety of adverse reactions,and the symptoms such as weakness,loss of appetite,as well as soreness in the waist often occur,causing the quality of life of patients difficult to improve.Therefore,it is urgent to find new treatments,intervene the progression and improving the quality of life of CUAN patients.In recent years,the advantages of Traditional Chinese Medicine(TCM)in the treatment of CUAN have become more prominent,meanwhile,the clinical trial and animal experiments have shown that Modified Simiao Decoction(MSD),the prescription which based on the method of promoting circulation and removing blood stasis,removing dampness and turbidity has achieved ideal curative effects in treating CUAN,and the tutor group also found that the TCM cream which functioned as replenishing spleen and kidney,stagnation and stagnation and turbidity also obtained efficacy in treating chronic renal failure patients with "spleen and kidney deficiency as well as dampness and phlegm obstruction",the symptoms such as abdominal fullness,backache and other symptoms were significantly relieved.Therefore,this research explored the clinical effects of herbal medicine for oral use and external application in treating CUAN.On the other hand,MSD is effective in the treatment of CUAN,but its curative mechanism is still unclear,therefore,this topic further explored the mechanism of MSD in the treatment of CUAN by metabolomics.Obj ective:1.Clinical trial:To observe the effect of MSD for oral administration combined with ointment rubbing on the treatment of CUAN patients with the type of spleen and kidney deficiency and dampness and phlegm obstruction,and further to analyze the changes of serum uric acid(SUA)and serum creatinine(Scr)between the two groups before and after treatment,to compare the therapeutic effect with the schedule of Western medicine combined with MSD orally.2.Animal experiment:To establish the rats model of CUAN,and draw the serum of rats after oral administration with MSD,further to systematically analyze the metabolomics between the contral group,the model group and the MSD group,and reveal the molecular mechanism of MSD in the intervention of CUAN at the metabolome level.Research method:1.Clinical trial:A total of 30 patients were involved,including the outpatient and inpatient hospital of the Third Affiliated Hospital of Beijing University of Chinese Medicine,who were diagnosed CUAN with the type of spleen and kidney deficiency and dampness and phlegm obstruction,and they were randomly and equally divided into control group and ointment group.The control group was given basic treatment of western medicine combined with MSD administration,and the ointment group further applied ointment rubbing.After 3 months,the SUA and Scr was compared between the two groups to evaluate the efficacy.2.Animal experiment:rats model of CUAN were induced by adenine combined with ethambutol.After successfully modeling,MSD was administered to intervene,and metabolomic analysis was administrated among the control group,the model group,and the MSD group.Research results:1.Clinical trials:(1)The SUA level significantly decreased in both the ointment group and the control group.Among them,and the SUA decreased by 29.80%(t=4.453,P=0.001),the control group decreased by 13.73%(Z=4.453,P= 0.001).(2)After treatment,the Scr level of the patients in the ointment group decreased by 34.78%(Z=-3.408,P=0.001),and Scr level appeared no statistically significant difference in the control group,but the Scr mean value decreased after treatment.(3)The total effective rate of the ointment group was 93.33%,which was higher than the total effective rate of the control group,which appeared 60.00%(P=0.01).(4)The total scores of TCM symptoms after treatment were significantly lower than those before treatment.The total score of symptoms in the ointment group decreased by 71.14%(t=19.572,P=0.00),and the control group decreased by 66.20%(t=14.981,P=0.00).The total effective rate was 100.00%in the ointment group and 93.33%in the control group,meanwhile the total effective rate of ointment group was higher than control group(P=0.00).2.Animal experiment:ultra-performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS)serum metabolomics analysis identified 42 potential pathological markers,including phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,phosphatidyl,after intervention with MSD Decoction.14 metabolites such as inositol and phosphatidyl serine showed significant down-regulation,and 28 differential metabolites such as tryptophan and guanidine showed significant up-regulation.Conclusion:1.Clinical trial:The therapeutic schedule that Western medicine basic treatment combined with MSD orally administration and ointment rubbing for CUAN patients of spleen and kidney deficiency,phlegm-dampness type has better effect in reducing SUA and Scr than orally administration only,and may reach more significant improvement in clinical symptoms.2.Animal experiment:There are disorders of metabolic pathways such as glycerophospholipid metabolism,tryptophan metabolism,pantothenate and coenzyme A synthesis in rats with CUAN,and MSD may protect residual kidney function by regulating the metabolic pathway of the above disorder. |
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