Study Of The Correlation Between Rheumatoid Arthritis And Atherosclerosis And The Mechanism Of Xinfeng Capsule On Improving Cardiac Abnormalities Caused By Rheumatoid Arthritis

Study the correlation between rheumatoid arthritis and atherosclerosis, study the mechanism of Xinfeng capsule on improving cardiac abnormalities of rheumatoid arthritis.1 ObjectiveTo study the correlation of rheumatoid arthritis and atherosclerosis, study the mechanism of Xinfeng capsule on improving cardiac abnormalities of rheumatoid arthritis.To reduce the probability of cardiovascular events in patients with rheumatoid arthritis, provide clinical theoretical foundation of traditional Chinese medicine treatment of rheumatoid arthritis(ra) cardiac lesion.2 Methods2.1 Theoretical research Collecting, sorting and reading a large number of relevant literature, to elaborate the relationship between rheumatoid arthritis, atherosclerosis, and the cardiac abnormalities, to elaborate related research actuality, indicate the significance of study the correlation of rheumatoid arthritis and atherosclerosis,and cardiac abnormalities.2.2 Clinical research The clinical data of 60 cases with rheumatoid arthritis who were diagnosis in Anhui province hospital rheumatism and then analyzed retrospectively by us. In addition,30 healthy check-up people were selected as a control group. These healthy check-up people were all come from Anhui province hospital physical examinationcenter. The object of study are tested age, sex, smoking, menopause, blood pressure,(BP), body mass index(BMI),and other clinical indicators. The intimal-medial thickness IMT of carotid artery and plaques were detected by GE Vivid- 7 color ultrasonic diagnostic instrument. The ankle brachial index(ABI)were detected by color doppler ultrasound blood flow detector.The PGI2 and TXA2 were detected by enzyme linked immunosorbent assay(ELISA). The TC 、 TC 、HDL-C、LDL-C were detected by automatic biochemistry analyzer.The ESR、CRP、RF、IgA、IgM、IgG、C3、C4 and other clinical indicators were detected by automatic biochemistry analyzer. To observe the signs and symptoms of joint, score of TCM symptoms, quality of life, health assessment questionnaire(HAQ), self-rating anxiety scale(SAS), self-rating depression scale(SDS) of patients with rheumatoid arthritis.Compare indicators of atherosclerosis in RA group and healthy controls, analysis the correlation between indicators by software SPSS19.02.3 Experimental research Totally 30 SD rats were assigned randomly into normal group(NC), model group(MC), Xinfeng capsule group(XFC), methotrexate group(MTX) and tripterygium wilfordii glycosides tablets group(TGT). All the rats were fed adaptively for 1 week, each rat was injected in posterior toes of subcutaneous with0.1 ml inflammatory freund’s complete adjuvant and obtain AA model except the NC group.These rats were given dose after 19 days from inflammation, each group dosing 30 consecutive days. Observe their body quality,the swelling of hind paw and the arthritis index(AI). Through the light microscope to observe their pathology morphologic lesions of joints and heart tissue. Observing their heart tissue lesions by electron microscopy.The levels of IL-6,IL-10 and TNF-ɑ in serum were analyzed by enzyme linked immunosorbent assay(ELISA).The NF-κB65、TNF-α of heart tissue were analyzed by real-time fluorescent quantitative PCR and Western blotting.3 Research results3.1 Theoretical research results3.1.1 The patients with rheumatoid arthritis possess higher disease incidence for atherosclerosis1) The lipid abnormalities in RA patients induced the As.2) The endothelium dysfunction in RA patients induced the As.3) The inflammation in RA patients increased arterial stiffness.4) The insulin resistance in RA patients induced the As.5) The abnormal immune in RA patients increased the As.3.1.2 RA patients with atherosclerosis is easy to cause heart disease1) Atherosclerosis accelerated the occurring of thrombus,and it causes myocardial necrosis.2) Atherosclerosis involving coronary artery increased cardiovascular events.3.1.3RA and heart impediment1) Heart impediment is closely related to spleen deficiency2) Heart impediment is closely related to emotion.3.2 Clinical research results3.2.1 Changes of basis, inflammation index in patients with RA The basis, inflammation index is significantly higher than healthy people.3.2.2 Changes of IMT in patients with RA The IMT of RA group is significantly higher than healthy people, RA patients withcarotid atherosclerosis and carotid atherosclerosis plaque formation is significantly higher than healthy people.3.2.3 Changes of ABI in patients with RA The ABI of RA patients was significantly higher than healthy people.3.2.4 Changes of vasoactive substances in patients with RA The level of PGI2 in RA patients was significantly lower than healthy people, the TXA2 of RA patients was significantly higher than healthy people.3.2.5 Changes of lipid levels in patients with RA There is abnormal metabolism of serum lipids in RA. The level of TG、LDL-C in RA patients were significantly higher than healthy people,and the level of HDL-C in RA patients was significantly lower than healthy people.3.2.6 The indicators in RA patients correlated with basis,inflammation index Analysis of correlation revealed that the IMT was correlated positively with age、course of disease、CRP;The ABI was correlated negatively with age、course of disease;The TXA2 was correlated positively with course of disease.3.2.7 The indicators in RA patients correlated with lipid Analysis of correlation revealed that the IMT was correlated positively with LDL-C,negatively with HDL-C; The ABI was correlated positively with HDL-C.3.2.8 The indicators in RA patients correlated with joint symptoms integral value, DAS- 28, TCM syndrome integral value Analysis of correlation revealed that the IMT was correlated positively with joint morning stiffness integral 、 less gas lazy words integral 、 less gas lazy wordsintegral;The ABI was correlated negatively with joint tenderness points、the time of walking 15m; The PGI2 was correlated negatively with the time of walking 15m;The TXA2 was correlated positively with hands grip strength of integral.3.2.9 The indicators in RA patients correlated with the quality of life:Analysis of correlation revealed that the IMT was correlated positively with physiological function, the PGI2 was correlated negatively with physiological function.3.2.10 The indicators in RA patients correlated with SAS、SDS Analysis of correlation revealed that the the IMT and the ABI was correlated negatively with SAS integral.3.3 Experimental research results3.3.1 Changes of body quality,the paw edema and the arthritis index(AI) in AA rats and the effect of XFC on it:The body quality of MC group was decreased significantly,and the paw swelling and the arthritis index was increased significantly compared with NC. The body quality of other treatment group rats was increased significantly, and the paw edema and the arthritis index was decreased significantly compared with MC. The body quality of XFC group was obviously higher than other treatment group.3.3.2 Changes of joint pathological morphology in AA rats and the effect of XFC on it:The structure of synovial membrane in NC group were clear, without hyperplasia and swelled, the structural of articular cartilage were integrity. The structure of synovial membrane in MC group were disorder, a large number of inflammatorycells infiltration in it, the structural of articular cartilage were coarse. The structure of synovial membrane in XFC group were basic clear, a few inflammatory cell infiltration infiltration in synovial membrane.3.3.3 Changes of heart tissue pathological morphology in AA rats and the effect of XFC on it:The structure of heart tissue in NC group was clear, there is no obvious pathological damage. The mitochondria in myocardium cells revealed edema,structural disorders with vacuolar degeneration and edematous myocardial fibers in MC group.The myocardial of XFC group basic regular, the swelling of cells was reduced after treatment.3.3.4 The ultrastructure of cardiac tissue was observed by transmission electron microscope.The myocardial cell membrane of NC group was integrity, the structure of the nucleus was complete, mitochondria was rich, mitochondrial cristae was close and arranged orderly, the structure was clear, a few of collagen fibers located between cells. The structure of the nucleus in MC group was in incomplete, mitochondrial cristae arranged disorder, a lot of collagen fibers located between cells. After treatment, The myocardial cell membrane of XFC group was basic integrity,sarcomere was regulation, a few of collagen fibers located between cells.3.3.5 Changes of cell factors of serum in AA rats and the effect of XFC on it:The level of IL- 6, TNF-a of MC group was increased significantly,and the level of IL-10 was increased significantly compared with NC. The level of IL- 6, TNF-a in XFC group was decreased significantly, and the level of IL-10 was increased significantly.3.3.6 Changes of the NF-κB/TNF-α signaling pathways of heart tissue and the effect of XFC on it:The level of NF-κB65、TNF-α was detected by real-time fluorescent quantitative PCR and Western blotting:The level of NF-κB65、TNF-α of MC group was increased significantly compared with NC. The level of NF-κB65、TNF-α of XFC group was increased significantly compared with MC.4 Conclusion4.1 The patients with rheumatoid arthritis possess higher disease incidence for atherosclerosis1) Even though the RA patients does not exist traditional cardiovascular risk factors,they still possess higher disease incidence for atherosclerosis than the general population.2)The high incidence of atherosclerosis in patients with rheumatoid arthritis may be related to RA patients with dyslipidemia and disorder of vasoactive factor.4.1.3The splenic asthenia of RA patients may increase the occurrence and development of atherosclerosis.3) Patients with rheumatoid arthritis associated with atherosclerosis easy to reduce the quality of life and increased patient.4.2 The effect of Xinfeng capsule on AA rats and their cardiac abnormalities.1) Xinfeng Capsule can significantly improve the quality of the body weight of AA rats, reduce their paw swelling degree and arthritis index,and there is no significant adverse reactions AA rats, and improving the quality of the body is better than theorther treatment group.2)Xinfeng capsule can significantly improve the level of IL-10, reduces the level of IL-6 and TNF-α, it can balance cytokine network of AA rat.3)Xinfeng Capsule can significantly improve the myocardial cell structure of AA rat,it can restrain the myocardial fibrosis of AA rat.4)Xinfeng Capsule can restrain the overactivation NF-κB/TNF-α signaling pathway of heart tissue, reduce the level of NF-κB65、TNF-α in heart tissue.4.3 The mechanism of Xinfeng Capsule improving cardiac abnormalities of AA rat.1) Xinfeng capsule regulate the cytokine network and reduce the immune inflammatory lesions of heart tissue.Xinfeng capsule can significantly improve the level of IL-10, reduces the level of IL-6 and TNF-α, it can balance cytokine network of AA rat, enhanced the ability of anti-inflammatory, restrain vascular endothelial function damage by inflammatory cytokines, improves cardiovascular diseases of AA rats,reduce the damage of heart tissue caused by immune and inflammatory.2) Xinfeng capsule regulate the protein of NF-κB/TNF-α signaling pathway and restrains the over-activation NF-κB/TNF-α signaling pathway.Xinfeng capsule can significantly improve the level of IL-10, reduces the level of IL-6 and TNF-α,restrains the over-activation NF-κB/TNF-α signaling pathway of heart tissue, improving cardiac abnormalities of AA rat.