| Rheumatoid Arthritis (RA) is a common and frequently-occurring disease in clinical Immune department of rheumatism. In1858,the British doctor Garrod first proposed the name of Rheumatoid Arthritis which is chronic and systemic disease basing on Synovial lesions. The manifestations of RA are mainly as extensive inflammation of connective issue including Synovitis, Serosal, Cardiopulmonary, skin, eyes and artery resulting in the damage of varieaty of organizations eg,Cartilage,Ligament,Tendon,Marrow and Multiple organs. The Synopsis may be recurrent causing the destruction of the Articular cartilage and bone and eventually leading to the joint deformity and destruction involving in multi-organ and multi-system diseaseofwhichPericarditis,Myocarditis,Pleurisy,Interstitial,pneumonia,Renal,amyloidosis,Eye disorders (eg:Scleritis,Iritis and so on) are commonly seen.RA is world recognized refractory disease.According to the foreign data,1% of population has the incidence of the this disease.On the ground of the survey in the North east China and BeiJing.Shantou, its incidence is about0.24%-0.5%.The incidence of RA has a wide range mainly between20-45yeas old of which80% are in35-50years old. Women are in higher incidence than men. The Incidence rate ratio of females and males is2-4?1. The pathogenesis is not entirely clear which may has close relation to the environment, bacterial, Virus, Autoimmunity, Hereditary, Sexhormones. In Chinese Medicine, RA belongs to Arthralgia and also called "Gu Bi"?'Kidney paralysis"?"LiJie"as the other name.RA is a common disease in now a days affecting our life qualify deeply which has a high morbidity and is a refractory common illnesses.1PurposeFrom the Chinese medicine point of view, man and nature should be in correspondence. Following its overall regulation as guidance and putting "kidney should be winter" as an entry point, the essay investigates the relationship between RA (a Chinese medicine category) Kidney deficiency and the season changes through animal experiments from the perspective of Melatonin high adjustment to reveal the material basis of kidney deficiency Arthralgia and the scientific nature of "the correspondence between the five internal organs and season" in a deeper way so as to provide experimental evidence and new target in molecular level for the Integrative treatment of RA to change the life quality of the patients.2Method2.1Theoretical StudyThe thesis is basing on the the document of the historical records also with the Chinese and Western medicine experimental findings of the RA Pathogenesis in the recent years while using the correlation of the season changes and the Kidney-type onset deposit as proof.Putting the nature of the Arthralgia incidence,the relation of the kidneys and the season changes in Chinese medicine view and the connection between the Arthralgia kidney type and the season changes as argument, combining the theory of the historical records and the modern experimental findings as proof,the thesis is to explain the correlation between the Arthralgia kidney deficiency and the seasonal changes.2.2Experimental study2.2.1Design ideasPutting the winter solstice and summer solstice as a starting point, the affect from the season changes to the RA kidney CD4+CD25+regulatory T cells can be observed through the experiment.2.2.2Research MethodsAdopting collagen ?-induced arthritis, CIA rat model which is the closest to the human RA clinical features,basing on the guidance of the Chinese medicine theory "man and nature should be in correspondence",the topic of the thesis researches the impact of season climate factors on the incidence of the disease and the pathological link. In the Winter Solstice and Summer solstice,the observation on the arthritis index of each rats group and the level change evaluation for the CD4+CD25+Treg/CD4+Treg content in the serum and the Cellular signal transduction index,Melatonin are being carried out while the Pathological observation for the rat knee and ankle joint tissue is also in progress.3Results3.1The theoreticalThe Chinese medicine believes that RA has some relation with wind-cold-wetness evil and lack of righteousness.The wind-cold-wetness evil is the external factor while deficiency is the internal factor which determines too much.Kidney deficiency is an important internal factor for the incidence of RA.The human body is an organic whole in which the five internal organs are as the center.In the internal of the whole,each part maintains self-dynamic equilibrium while it also has a constant exchange of material and information with the external environment. The research in nowadays has proved the scientific nature of the "The kidney corresponding to the winter"and the influence from season to the normal operation of the kidney functions.Basing on the theory of correspondence between time and zang-organ "the kidney generating marrow and dominating bone"?"corresponding to the winter",after a large number of clinical or experimental studies,it proves that Kidney deficiency, winter,and the incidence of RA has a close relation. 3.2The experiment3.2.IRA Model replicationBasing on the idea of combination of disease and syndrome,the model of rheumatoid arthritis, CIA can be replicated by Collagen type II and the kidney deficiency type model can be replicated by the way of removing the gonads.During the feeding observation,compared with the other groups of the model.,the hind limbs of the rats whose gonads have been removed are more severe in joint swelling and even deformation also accompanied by listlessness,unresponsive,burnout curled,hair removal and the phenomenon of loose stools.It is in accordance with the symptom of kidney deficiency which proves the successful simulation of the kidney deficiency model.From the result of the experiment for the incidence of RA in winter and summer,the RA incidence in the model of rheumatoid arthritis, CIA in winter and the sham-operation rat group is higher than in summer. RA incidence in winter is higher in summer for the operation group, but the difference is not so clear.The reason is that the operation group has made their Pineal gland removed.,which made them lose the medium expressing the rhythm between human and nature.All of this persuades that the RA incidence or aggravation is commonly seen in winter which is also proves Pineal gland-melatonin is an important organ to express the body's natural rhythm.3.2.2The observation in the view of Pathological morphologyCompared to the CIA group and sham-operation group,the knee and ankle joint fsynovial connective tissue of the operation group proliferate severely and become thick or the proliferation cartilage connective tissue filles with joint cavities or even connect to the surface of both sides of the articular cartilage to make the joint cavity become narrow. The edge of the articular cartilage is not jagged so the peeled articular cartilage and the proliferation cartilage connective tissue can be visible in the Joint cavity. The most serious one is the the bone marrow cavity expansion. The amount of bone marrow is greatly reduced and the infiltration of a large number of inflammatory cells can be seen.The nucleus is not standardized and the mast cells disappear while the fat cells are rare. The marrow cavity expands apparently or there is calcification formed. All of this proves that the kidney deficiency increases the lesion of RA and the destruction of the bone joint eventually lead to the symptoms of RA get worse. Kidney deficiency is an important internal cause of RA.3.2.3CD4+CD25+regulatory T cells expressing the resultsCompared with the normal group rat, the CD4+CD25+Treg/CD4+Treg levle of the model of rheumatoid arthritis, CIA group,operation group, and the sham-operation group was significantly decreased and the difference has statistics significance.it proves that RA can lead to the decrease of the treg level.In the season comparison,the treg level of the winter normal group,the model of rheumatoid arthritis, CIA group and the sham operation group is lower than the summer group which has statistics significance.because of the removal of the Pineal gland,the treg level for the operation group has no difference in summer and winter which means the change of the treg level has nature rhythm.and the immunity of the body in winter is lower than summer.all of the above is consistent with with the traditional Chinese medicine theory---in winter Yang is hidden inside.3.2.4The Assay results of Serum of IL-i?, IL-6Compared to the normal group,the IL-1??IL-6level of the other groups has increased in differently.the operation group is in higher level than the others and the difference has statistics significance.it proves that the revoval of the Gonad has caused the kidney deficiency involving in the increase of the CytokinesIL-1??IL-6level leading to the intensity of the Inflammatory response and aggravating the progression of RA so kidney deficiency is the root cause of RA.Comparing to the winter and summer,the level of IL-1??IL-6of the CIA model group and sham operation group is higher significantly in winter.the difference has statistics significance.it shows the IL-1??IL-6level of RA has the winter high and the summer low trend which reflects the Chinese medicine theory of correspondence between time and zang-organ.3.2.5The test results of the Melatonin (MT) contentThe Serum MT level of the four experimental group is different. Compared with the normal group, the model of rheumatoid arthritis, the level of the CIA group and the sham operation group is significantly high while the level of the operation group is lower than the others.the difference has statistics significance.It shows that MT increases the incidence of RA and its exacerbation indirectly which proves the close link between melatonin and the pathogenesis of RA.Fort the determination of the results for winter and summer MT levels,the Serum MT content of the Physiological group,CIA model group,and the Sham operation group in winter increased significantly than in summer.The difference has statistics significance.The Serum MT of the operation group doesn't has clear difference between winter and summer. The MT level shows low trend in winter and high in summer which has a unity with nature.and is in accordance with the Chinese medicine theory---man and nature should be in correspondence.4ConclusionsAll of above shows: ?The combination of collagen II-induced arthritis, CIA and removal of gonad can replicate RA kidney deficiency model successfully.The incidence of this disease is higher in winter than in summer.Pineal gland-melatonin is an important organ to express the body's natural rhythm.?From the pathological morphology and the result of the Semi-quantitative analysis to the destruction of the knee and ankle joint in groups,the ankle destruction of the operation group is more serious which means kidney deficiency increases the lesion of RA and the destruction of bone joint to make RA become serious and it is the internal cause of RA.All of above is consistent with the Chinese medicine theory---the kidney generating marrow and dominating bone.?Compared to the normal group,the CD4+CD25+Treg/CD4+Treg level of the other group reduces clearly.The treg level of the winter normal group,CIA model group and sham-operation group is lower than the summer group.It shows the summer high and winter low trend. The immunity of our human is low in winter which is consistent with the Chinese medicine theory.?IL-1??IL-6has positive correlation with RA which is a diagnostic indicator of RA incidence.The IL-1??IL-6of the operation group is higher than the other group.it means Kidney deficiency is an important internal cause of RA.The level of IL-1??IL-6of the CIA model group and sham operation group shows the winter high and summer low trend which means the RA incidence is higher in winter.?The MT level of the RA rat group is higher than the normal group which means MT has stimulated and accelerated the incidence of RA.Except the operation group, the MT level of the other group shows the trend of winter high and summer low which means the Pineal gland-melatonin is an important index for human body to show the nature rhythm changes. All of this proves the scientific nature of the Chinese medicine theory---human and nature should be in corresponding.In summary,the experiment based on the theoretical and experimental study proves that kidneydeficiency-RA,humanbody-season-RA,humanbody-Pinealgland(melatonin)-season,RA-season-Regulatory T cells has corresponding in nature which can provide new evidence and basis for the further study of RA Pathogenesis and Clinical treatment of RA. |
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