| Purpose:To explore the risk factors,intraluminal imaging characteristics and prognosis of coronary artery disease in patients with Takayasu arteritis;To explore the dialectical typing of Takayasu arteritis and the rule of TCM treatment,and to evaluate the treatment ofdiseases by Tongmai method of TCM;To explore the effect of Wenyangtongmai Decoction on rat arteritis.Material and method:1.A retrospective study of aortitis involving coronary artery disease:1.1Risk factors of coronary artery disease in patients with Takayasu arteritis: 442 cases were included.According to the situation of coronary artery involvement,the patients were divided into two groups: group A: Takayasu arteritis involved coronary artery disease(at least one coronary artery stenosis(≥50%)and group B: Takayasu arteritis did not involve coronary artery.Logistic regression model was used to analyze the risk factors of arteritis involving coronary artery lesions.1.2Clinical and intraluminal imaging features of coronary artery disease associated with Takay-asu arteritis:125 patients(group A)with coronary artery involvement were enrolled.125 patients(group B)with atherosclerotic heart disease without TA in the same period were selected as matching condition 1:1.Coronary angiography or coronary CTA were performed to calculate Gensini score.The differences of intraluminal imaging OCT imaging between the two groups were observed and ESR,hs CRP,and CTA were detected.Scr,TC,LDL-C,HDL-C and TG levels were estimated by CKD-EPI equation.The occurrence of MACE after discharge was recorded,including death,recurrent myocardial infarction,angina pectoris and heart failure.The differences between the two groups were compared.1.3Prognosis of TA involving coronary artery lesions in different treatment methods:125patients of Takayasu arteritis involving coronary artery disease were divided into three groups according to different treatment methods: group A was treated with drugs,group B was treated with interventional therapy,and group C was treated with coronary artery bypassgrafting.Follow-up was conducted by telephone follow-up,outpatient re-visit and inpatient medical record system.The occurrence of MACE after discharge was recorded,including death,recurrent myocardial infarction,angina pectoris,heart failure,restenosis and coronary revascularization.Cox regression model was used to analyze the risk factors associated with MACE.2.Literature study on the treatment law of traditional Chinese medicine and systematic evaluation on the treatment of Takayasu arteritis with Tongmai method:2.1Study on the Regularity of TCM Treatment of Takayasu Arteritis:China National Knowledge Infrastructure Database(CNKI),Wanfang Database,Chongqing VIP Database(VIP),China Biology Medicine Database(CBM),MEDLINE(Pubmed),and Cochrane Library were retrieved with the deadline on July 1,2017.The Chinese search terms are "Takayasu","Maibi","Wu Mai Zheng" "Vascular arthralgia";English search terms are"Takayasu","Maibi","Wu Mai Zheng" "Vascular arthralgia".Search for books such as"Medical Intensive Reference to Western Records","Ye Tianshi’s Medical Records" and"Medical Records of Famous Medium-modern Doctors".Documents on "Takayasu"," Maibi",and ""Wu Mai Zheng " in TCM or TCM or TCM-WM dialectics,classification,treatment and diagnosis of Takayasu Arthritis are included in the literature.Discuss the syndrome type of Takayasu arteritis and the rule of traditional Chinese medicine treatment.2.2Meta-analysis of Tongmai Therapy for Takayasu Arthritis: China National Knowledge Infrastructure Database(CNKI),Wanfang Database,Chongqing VIP Database(VIP),China Biology Medicine Database(CBM),MEDLINE(Pubmed),and Cochrane Library were retrieved with the deadline on July 1,2017.The Chinese search terms are" Tongmai ","Takayasu","Maibi","Wu Mai Zheng" "Vascular arthralgia";English search terms are "Tongmai ","Takayasu","Maibi","Wu Mai Zheng" "Vascular arthralgia".The control group was treated by routine treatment,while the experimental group was treated by routine treatment plus a randomized controlled trial based on Tongmai method to evaluate the curative effect of Tongmai method of traditional Chinese medicine on diseases.Jadad scoring table was used for literature quality evaluation,Cochrane System Review Manual bias risk assessment criteria were evaluated,and Rev Man 5.3 software was used for meta-analysis.3.Experimental study on the effect of Wenyangtongmai Decoction on rat arteritis: 60 female SD rats were selected and randomly divided into normal group,model group,low dose group,middle dose group,high dose group and hormone group according to body weight.The diethylstilbestrol suspension was administrated at a dose of 2mg / kg /d for 90 days,twice a day.Rats in the normal group were given 2 mg / kg / d normal saline daily for 90 days,twice a day,to establish the rat arteritis model.The animal model was evaluated by observing the general situation,the morphological changes of the great arteries and the results of HE staining.After the model was established successfully,the drug was given to Wenyangtongmai decoction,and the stomach was infused at a fixed time in the morning every day.The normal group and the model group were given the same amount of normal saline.The other groups were given the corresponding intervention drugs for 30 days,twice a day.At the end of the experiment,blood was taken from the abdominal aorta,and then the thoracic aorta was cut off,washed with normal saline,and stored in 4% paraformaldehyde solution at 4 ℃.Detect ESR and TNF-α,IL-6,CRP were detected by ELISA.The aortic specimens were paraffin embedded to make pathological sections HE staining.The expression of NLRP3 and IL-18 was detected by SABC immunohistochemistry.Results:1.A retrospective study of aortitis involving coronary artery disease:1.1 Risk factors of coronary artery disease in Takayasu arteritis:1.1.1Among 442 TA patients,125(28.2%)were involved in coronary artery disease.There were 80 males and 362 females,and the ratio of males to females was about 1:4.5.Compared with those without coronary artery involvement,patients with TA involvement were older(52.54±11.17 vs 37.73±12.72,P < 0.001),older(42.21±11.46 vs 32.74±13.13,P < 0.001),longer(5.0 vs 1.0,P < 0.001),and had larger BMI(24.17±3.31 vs 22.99±3.92,P=0.002),and had higher rates of smoking,drinking,diabetes and dyslipidemia.The differences were statistically significant(all P < 0.05);the proportion of heart murmurs and vascular murmurs in physical signs was more significant(P < 0.001);the level of e GFR was significantly decreased(91.96±25.71 vs 106.49±24.59,P < 0.001),UA and TG levels were significantly increased,and the differences between the two groups were statistically significant(P < 0.05).1.1.2Regarding whether TA involved coronary artery as dependent variable and sex,age,age of TA onset,course of TA,BMI,smoking history,drinking history,hypertension,dyslipidemia,diabetes mellitus and disease activity as independent variables,the results showed that age of TA onset(OR = 1.143,95% CI: 1.007-1.298,P = 0.039),course of TA(OR = 1.165,95% CI: 1.025-1.324,P = 0.020),BM.I(OR = 1.100,95% CI: 1.021-1.185,P =0.013)were all risk factors for TA involving coronary artery.1.2Clinical and intraluminal imaging features of coronary artery disease associated with Takayasu arteritis1.2.1 Compared with coronary heart disease group,TA involved more women in coronary artery disease group,while BMI smoking,drinking,diabetes and DBP,MAP decreased significantly(P < 0.01);cardiac murmur and vascular murmur were more in physical signs(P< 0.001);beta-blockers,ACEI/ARB drugs,aspirin in clinical use were more significant(P <0.001).The proportion of statins and clopidogrel was significantly reduced,with statistical significance(P < 0.001);the levels of Hb,UA,TG and LDL-C were significantly decreased,while the levels of HDL-C were significantly increased(all P < 0.05).1.2.2 Characteristics and distribution of coronary artery lesions: A total of 237 stenosis lesions were found in TA involving coronary artery lesion group,of which 153(64.56%)were involved in open and proximal coronary artery lesions,and 59(24.9%)were involved in open coronary artery lesions.Compared with the coronary heart disease group,the proportion of open lesions in TA involving coronary artery disease group increased significantly(24.9%vs 8.7%,P < 0.001),and the proportion of middle and distal lesions decreased significantly(32.5% vs 48.3%,P < 0.001)and(3.0% vs 7.6%,P = 0.018),respectively.1.2.3 Intravascular image OCT imaging features: TA involvement of coronary artery lesions OCT imaging features severe fibrointima thickening,imaging for high reflection,strong signal,low attenuation,homogeneous texture;visible flake-like signal areas stronger than surrounding tissues,radiation shadow behind,suggesting macrophages;and visible intraluminal uncoupled non-signal lumen structure,mentioned.It is shown as a microchannel.The characteristics of coronary atherosclerotic plaque OCT imaging are as follows:atherosclerotic lipid plaque imaging is low reflection,weak signal,high attenuation,opacity,uniform texture,unclear boundaries.1.2.4 Prognosis: Compared with CHD group,the incidence of recurrent angina pectoris(28.5% vs 14.9%,P = 0.010),heart failure(8.1% vs 2.5%,P = 0.049)and overall MACE(42.3% vs 22.3%,P = 0.001)in TA group were significantly higher than those in CHD group.1.3Prognosis of TA involving coronary artery lesions in different treatment methods:1.3.1Among 125 patients,55(44.0%)received conservative drug therapy,57(45.6%)received PCI and 13(10.4%)received CABG.The age of onset in CABG group was older than that in drug treatment group and PCI group,with statistical significance(P < 0.05);the level of HDL-C in CABG group was significantly higher than that in drug treatment group and PCI group,with statistical significance(P < 0.05);the level of ESR in PCI group and drug treatment group was higher than that in CABG group,with statistical significance(P <0.05);the incidence of recurrent angina pectoris,restenosis and MACE in PCI group was significantly higher than that in CABG group(P<0.05);The rate of coronary revascularization in CABG group was significantly higher than that in drug therapy group and CABG group(P < 0.05).1.3.2 Multivariate Cox regression analysis showed that disease activity(OR = 13.056,95% CI:3.835-44.455,P < 0.001),TA course(OR = 1.065,95% CI: 1.023-1.109,P = 0.002),interventional therapy(OR = 3.475,95% CI: 1.324-9.121,P = 0.011)were all risk factors for MACE in patients with coronary artery involvement.2.Literature study on the treatment law of traditional Chinese medicine and systematic evaluation on the treatment of Takayasu arteritis with Tongmai method:2.1Study on the Regularity of TCM Treatment of Takayasu Arteritis2.1.1 Document retrieval results: A total of 109 literatures were collected,including 13 main syndromes,10 main prescriptions,18 main traditional Chinese medicines and 2 other treatments.2.1.2 Dialectical typing: In the dialectical typing of Takayasu Arteritis,deficiency of both qi and blood is the most common,occurring frequency is 9 times,frequency is 1.63%,Yin deficiency and internal heat syndrome is the least,frequency is 6 times and frequency is1.09%;the syndrome of dampness,toxin and blood stasis is the most frequent,frequency is81 times,frequency is 14.70%,followed by dampness-heat stagnation syndrome andphlegm-blood stasis syndrome,frequency and frequency are 72(13.07%),71(12.89%),cold coagulation pulse syndrome,Phlegm Blood Stasis syndrome,respectively.Qi stagnation and blood stasis syndrome and heat toxin blocking collateral syndrome occur less than 70 times;Yang deficiency and cold coagulation syndrome is the most common type of deficiency and excess syndrome,the frequency is 58,the frequency is 10.53%,followed by Qi deficiency and blood stasis syndrome,the frequency is 48,the frequency is 8.71%,Yin deficiency and phlegm blocking syndrome,Yin deficiency and yang hyperactivity syndrome occurs the least,the frequency,frequency,frequency is 11(7.2%);other syndromes appear less,a total of 4times,the frequency is 0.66%.2.1.3Prescription statistics: The main prescriptions in the selected literature are 9 prescriptions,7 prescriptions from the author and 7 empirical prescriptions.The main prescriptions listed are Wenyang Tongmaitan and Huangqi Guizhi Wuwu Tang.The frequency and frequency of the prescriptions are 89(24.25%),81(22.07%),respectively;Yanghe Tang and Buyang Huanwu Tang are next,the frequency and frequency are 49(13.35%),41(11.17%),respectively.The frequency and frequency of Xuefu Zhuyu Decoction,Simiao Yongan Decoction were 28(7.63%),20(5.45%),respectively;the frequency and frequency of Huoxue Tongmai Decoction,Zhenggan Xifeng Decoction and Tianma Gouteng Teng Decoction were 18(4.90%),16(4.36%)and 12(3.27%),respectively;finally,Guipi Decoction frequency and frequency were 7(1.91%),and other prescriptions appeared less,totally 6 times,the frequency was 1.63%.2.1.4 Statistics of TCM: There are more than 20 flavors of TCM in the literature,with a total frequency of 693.Glycyrrhiza uralensis,with a frequency of 358 and 13.29%;Astragalus membranaceus,with a frequency of 298(11.07%);then Angelica sinensis,Cassia twig and Paeonia rubra,with frequencies of 261(9.69%),225(8.35%),213(7.91%).2.1.5 The clinical effective rate of Chinese medicine in the treatment of Takayasu arteritis:There were 5182 patients in 109 articles,including 1927 cases in the experimental group,1756 cases in the control group and 1499 cases in the control group before and after treatment.There were 2314 males and 1834 females,aged 41.85 + 10.42,and the course of treatment was 11.24 + 5.82 days.The clinical cure rate of traditional Chinese medicine in the treatmentof Takayasu arteritis showed that in the control trial,the effective rate was 85.16% and the ineffective rate was 14.84%,while in the control group,the effective rate was 65.21% and the ineffective rate was 34.79%.The effective rate was 86.99% and the ineffective rate was13.01%.In conclusion,the total effective rate of TCM in the treatment of Takayasu arteritis is85.96%,which is significantly higher than that of the control group and the self-control group(p < 0.01),indicating that TCM has a definite effect in the treatment of Takayasu arteritis.2.2 Meta-analysis of Tongmai Therapy for Takayasu Arthritis: A total of 438 subjects were enrolled in 9 studies.The effective rate of Tongmai Therapy for improving the clinical symptoms of Takayasu Arthritis was 2.85 [1.60,5.08];the effective rate of erythrocyte sedimentation rate(95% CI)was-4.11 [-5.31,-2.91];the effective rate of C-reactive protein(95% CI)was-3.65 [-4.30,-3.01];and the effective rate of anti-O(95% CI)was-50.78[-52.62,-48.95].3.Experimental study on the effect of Wenyangtongmai Decoction on rat arteritis:3.1model evaluation: in the model group,there were obvious thickening and hardening changes in the aortic wall,uneven surface of intima and plaque like protrusion.He staining:under the light microscope,the outer membrane wall of the aorta was thickened,the whole arterial wall was infiltrated with lymphocytes and plasma cells,and the connective tissue was proliferated;the middle membrane was myxoid,and smooth muscle cells were proliferated;the inner membrane was thickened,collagen fibers were increased,and the inner elastic plate was broken and disappeared.3.2 comparison of HE staining results: Compared with the normal group,the model group showed inflammatory cell infiltration in the aortic wall,myxoid degeneration in the middle membrane and elastic plate destruction,so it had obvious changes compared with the normal group;in the hormone group and the high-dose group of traditional Chinese medicine,the arrangement of the elastic membrane was more regular,part of the outer membrane thickened,myxoid degeneration appeared in the middle membrane,inflammatory cell infiltration was seen,and the inner membrane was slightly uneven,so the hormone group and the middle membrane There was no significant difference between the high-dose group and the normal group,and there was significant difference between the high-dose group and the model group;most parts of the inner,middle and outer membranes of the aorta in the middle and low-dosegroups of traditional Chinese medicine appeared pathological changes,and there was significant pathological changes with the normal group,hormone group and high-dose group of traditional Chinese medicine,but it was better than the model group3.3 Immunohistochemical staining of NLRP3 and IL-18: compared with the normal group,the expression of NLRP3 and IL-18 in the model group,the low dose group and the middle dose group of traditional Chinese medicine increased(P < 0.01);compared with the model group,the expression of NLRP3 and IL-18 in the hormone group,the high dose group and the middle dose group decreased(P < 0.01,P < 0.05);compared with the hormone group,the expression of NLRP3 and IL-18 in the high dose group of traditional Chinese medicine had no statistical difference(P > 0.05)The expression of NLRP3 and IL-18 in the middle dose group and low dose group was higher than that in the high dose group(P < 0.01).3.4 comparison of ESR results: compared with the normal group,the ESR of the model group,the low-dose group and the middle dose group increased significantly(P < 0.01,P < 0.05),but there was no statistical difference between the hormone group and the high-dose group(P > 0.05);compared with the model group,the ESR of the hormone group,the high-dose group and the middle dose group decreased significantly(P < 0.01);compared with the hormone group,the high-dose group had no statistical difference.Compared with the high dose group,the ESR of the low and middle dose group increased significantly(P < 0.01,P <0.05);compared with the high dose group,the ESR of the low and middle dose group increased significantly(P < 0.01,P < 0.05);compared with the middle dose group,the ESR of the low dose group increased significantly(P < 0.05).3.5 comparison of CRP results: compared with the normal group,the CRP content in the model group,the low-dose group and the middle-dose group increased significantly(P <0.01),but there was no statistical difference between the hormone group and the high-dose group(P > 0.05);compared with the model group,the CRP content in the hormone group,the high-dose group and the middle-dose group decreased significantly(P< 0.01);compared with the hormone group,there was no statistical difference between the high-dose group and the high-dose group.Compared with the high-dose group,the CRP content in the low-dose group was significantly higher(P < 0.01,P < 0.05);compared with the low-dose group,the CRPcontent in the low-dose group was significantly higher(P< 0.01,P< 0.05);compared with the middle-dose group,the CRP content in the low-dose group was significantly higher(P< 0.05).3.6 comparison of IL-6 results: compared with the normal group,the content of IL-6 in the model group,the middle dose group and the low dose group increased significantly(P < 0.01),but there was no statistical difference between the hormone group and the high dose group(P > 0.05);compared with the model group,the content of IL-6 in the hormone group,the high dose group and the middle dose group decreased significantly(P< 0.01);compared with the hormone group,there was no statistical difference between the high dose group and the high dose group The difference(P>0.05),the content of IL-6 in middle dose group and low dose group increased significantly(P<0.01);compared with high dose group,the content of CRP in low and middle dose group increased significantly(P< 0.01,P< 0.05);compared with middle dose group,the content of IL-6 in low dose group increased significantly(P < 0.05).3.7 comparison of TNF-α results: compared with the normal group,the content of TNF-α in the model group,the middle dose group and the low dose group increased significantly(P <0.01),but there was no significant difference between the hormone group and the high dose group(P > 0.05);compared with the model group,the content of IL-6 in the hormone group,the high dose group and the middle dose group decreased significantly(P < 0.01);compared with the hormone group,the high dose group had no statistical significance.The content of ESR in middle dose group and low dose group was significantly higher than that in high dose group(P < 0.01,P < 0.05).Conclusion:1.The later the age of TA onset,the longer the course of TA,and the more traditional risk factors of atherosclerosis in TA patients,the more susceptible they are to coronary artery involvement,and may not be related to the disease activity in clinical;The lesions of TA involved in the coronary artery are mostly seen in the opening and near segment of the coronary artery.OCT imaging can accurately show the characteristics of the lesions and identify the cause of coronary artery stenosis.The prognosis of TA patients with coronary artery disease was worse than that of the same age group,and the recurrent angina and heart failure were more common.The course of TA,disease activity and PCI are the independentrisk factors for the poor prognosis of TA involving coronary artery disease.2.Tongmai method of traditional Chinese medicine can inhibit the inflammatory reaction of the body and has definite effect on the treatment of Takayasu arteritis.3.Wenyangtongmai decoction can regulate immunity,inhibit inflammatory reaction of TA rats,and effectively alleviate the condition of aortitis.It can be considered as one of the treatment methods of aortitis. |
