Effects Of High-Fat Diet On Clinical Characteristics And Pathological Changes Of Synovitis In Rabbits

As a disease with high incidence worldwide,osteoarthritis is one of the major causes of disability.Osteoarthritis has a serious impact on the joint health of humans and animals,but also affected the development of animal husbandry and aquaculture.As one of the pathological changes of osteoarthritis,synovitis often causes persistent pain,so it is very important to study the influencing factors of synovitis.Obesity is one of the known potential risk factors for osteoarthritis,but there are few studies on the association between synovitis and obesity.The purpose of this study was to investigate the effects of high fat diet on the occurrence and development of synovitis and osteoarthritis by dynamically observing the pathological characteristics of synovitis and the changes of synovial macrophages in rabbits with knee osteoarthritis.Thirty-six New Zealand white rabbits were randomly divided into three groups:control group(Group C),high-fat diet group(Group H),osteoarthritis group(Group OA)and high-fat diet-osteoarthritis group(group HO),9 in each group.The osteoarthritis model was established by papain injection of 0.1 m L of 4%papain solution into the medial space of the knee joint every three days.After modeling,the rats were weighed,the knee width was measured,and the pain score was scored.Blood was collected from ear vein once and centrifuged,and the serum was stored at-80℃.the right knee joint was photographed by X-ray,and the change of knee joint space was detected by X-ray.Three rabbits in each group were killed at 4,8 and 12 weeks after modeling,and samples(liver,synovium and cartilage)were collected and fixed with paraformaldehyde,then prepared the paraffin sections and observed the liver by HE staining,the pathological changes of synovium and cartilage were evaluated by Kreen method;The concentrations of serum C1M and C3M,cholesterol,adiponectin and leptin were detected by ELISA;and the concentrations of IL-1β,IL-6 and TNF-αin synovial membrane were detected by Westernblotting;The changes of IL-1β,IL-6 and TNF-αin synovial membrane were detected by fluorescence quantitative method;The polarization of macrophages was observed by immunofluorescence staining of type M1 and type M2 macrophages in paraffin section of synovium.The results showed that body weight and serum TC concentration in H group were significantly higher than those in control group.The width and pain score of the right knee in OA group were significantly higher than those in the control group.He-stained sections of cartilage and synovium showed many inflammatory cells,chondrocyte clusters and synovium lining cells.The knee width and pain scores before 6 weeks in HO group were lower than those in OA Group.X-ray and synovial scores showed the same trend;At 12 weeks,the knee width,pain score and synovial Kreen score in HO group were significantly higher than those in OA Group.At the 4th week,serum C1M and C3M concentrations in HO group were significantly higher than those in C group,but significantly lower than those in OA Group.The serum concentrations of C1M and C3M in OA group were significantly higher than those in OA Group at the 12th week.The concentrations of IL-1β,IL-6 and TNF-αin synovium also showed the same trend.Compared with OA Group,the levels of inflammatory factors in HO group decreased at the 4th week and increased at the 12 week after high-fat diet administration.At the 4th week after modelling,the number of macrophages in OA group was significantly higher than that in HO group,and the number of CD38~+macrophages in OA group was significantly higher than that in CD206~+.On the contrary,the number of CD206~+macrophages in HO group was significantly higher than that in OA group.At the 12th week after modeling,the number of macrophages in the OA group decreased significantly compared with week 4.The number of macrophages in HO group at the 12th week increased significantly compared with week 4,and the number of CD38~+macrophages was higher than that of CD206~+macrophages.According to the above results,we can draw the following conclusions:(1)high-fat diet can reduce the levels of IL-1β,IL-6,TNF-αand MMP-3 in synovium at the early stage of osteoarthritis,and slow down the synovial inflammation at the early stage of osteoarthritis;(2)long-term high-fat diet could increase the levels of inflammatory factors such as IL-1β,IL-6,TNF-αand MMP-3 in the synovium of OA,increase the concentrations of lipid factors such as LEP and ADP in serum,and aggravate the clinical symptoms of OA,and then aggravate synovial inflammation of OA;(3)long-term high-fat feeding can induce synovial macrophages to transform from anti-inflammatory type M2 macrophages to pro-inflammatory type M1 macrophages,and aggravate synovial inflammation.