| Objective: To investigate the activationthe of diets rich in different types of fatty acids on the onset of osteoarthritis(OA)in obese mice induced by high-fat diet after DMM surgery,and the role of TLR4/My D88/NF-κB signaling pathway in it.Provide theoretical basis for nutritional prevention and treatment of obesity-related OA.Methods: 50 male C57BL/6 mice were devided into 5 groups randomly,each with 10animals: control group(LD),saturated fatty acid group(SFA),monounsaturated fatty acid group(MUFA),n-6 polyunsaturated fatty acid group(N6)and n-3 For the polyunsaturated fatty acid group(N3),the control group was fed ordinary feed,and the other groups were fed high-fat feed rich in different types of fatty acids.On the18 th week,all mice underwent destabilization of medial meniscus surgery(DMM)on the right hind limbs and sham surgery on the left hind limbs,and then continued feeding until 26 weeks.Histopathological staining combined with behavioral detection to evaluate OA.The level of serum IL-1β was determined by ELISA.Cartilage protein was extract and the expression level of TLR4/My D88/NF-κB signaling pathway were determined by Western blot.Result:1.High-fat diet with different types of fatty acids and the effects of different types of fatty acids on body weight,food intake and body fat ratio in mice During the experiment,the weight of each high-fat group was significantly higher than that of the control group(P<0.05),and there was no difference between the high-fat groups.The weight after DMM decreased,but the previous trend was restored.At the end of the experiment,the weight of each high-fat group It was still significantly higher than the control group(P<0.05).The weight of the SFA and MUFA groups was significantly higher than that of the N6 and N3 groups(P<0.05);the food intake of each high-fat group was lower than that of the control group(P<0.05),but each was higher There was no statistical difference in the food intake of the fat group;the body fat ratio of each high-fat group was higher than that of the control group(P<0.05),and the body fat ratio of the SFA and MUFA groups was significantly higher than that of the N6 and N3 groups(P<0.05).2.High-fat diet with different types of fatty acids and the effects of different types of fatty acids on OA In sham,compared with the LD group,the pathological changes of the mice in the SFA and N6 groups were severe,while the MUFA and N3 groups had no significant changes.The Mankin score and OARSI score showed that the high-fat group was higher than the LD group.It is statistically significant(P<0.05),the SFA group and N6 group are significantly higher than the MUFA group and N3 group(P<0.05);In DMM,compared with the LD group,the pathological changes in the joints of the mice in the SFA and N6 groups were severe,but there were no significant changes in the MUFA group and the N3 group;the Mankin score and the OARSI score showed that the SFA group,MUFA group,and N6 group were all high In the LD group,the difference was statistically significant(P<0.05).The Mankin score and OARSI score of the SFA group and the N6 group were significantly higher than the MUFA group and the N3 group(P<0.05).In addition,the Mankin score and OARSI of the MUFA group The score was significantly higher than that of the N3 group(P<0.05);Compared with sham operated joints,the scores of DMM operated joints in the LD group,MUFA group and N6 group were significantly higher(P<0.05).The gait analysis results showed that compared with the LD group,the SFA group,the MUFA group,and the N6 group had irregular footprints,and the footprint area,maximum footprint contact and support ratio were significantly reduced,and the swing speed(cm/s)was significant increase(P<0.05).3.The effect of high-fat diet with different types of fatty acids and different types of fatty acids on the expression of serum inflammatory factor IL-1βCompared with the LD group and the N3 group,the expression of the inflammatory factor IL-1β in the serum of the SFA group,the MUFA group and the N6 group increased,and the difference was statistically significant(P<0.05);the SFA group and the N6 group IL-1β The level was significantly higher than that of the MUFA group and the N3 group(P<0.05).4.Effects of high-fat diet with different types of fatty acids and different types of fatty acids on the expression of TLR4,My D88,and NF-κB in mouse articular cartilage In sham,compared with the LD group,the expression levels of TLR4,My D88,and p-NF-κB in the SFA,MUFA and N6 group were significantly increased(P<0.05),and the My D88 expression in the N3 group was significantly increased(P<0.05);Compared with the SFA group,the expression of TLR4 in the MUFA group and the N6 group was significantly increased(P<0.05),and the expression of My D88 and p-NF-κB in the N3 group was significantly reduced(P<0.05),compared with the MUFA group In comparison,the expressions of TLR4,My D88 and p-NF-κB in the N3 group were significantly reduced(P<0.05).Compared with the N6 group,the expressions of My D88 and p-NF-κB in the N3 group were significantly reduced(P<0.05).In DMM,compared with the LD group,the expression levels of TLR4,My D88,and p-NF-κB in the SFA,MUFA and N6 group were significantly increased(P<0.05);compared with the SFA group and the MUFA group Compared with the N3 group,the expression of TLR4,My D88 and p-NF-κB protein were significantly reduced(P<0.05).Compared with the N6 group,the expression of TLR4 and My D88 in the N3 group was significantly reduced(P<0.05).Compared with sham-operated joints,in DMM-operated joints,the expression levels of TLR4,My D88,and NF-κB in SFA,MUFA,and N6 groups were up-regulated(P<0.05),but there was no significant change in N3 group(P>0.05).Conclusion:1.DMM can accelerate the process of OA in mice.2.A high-fat diet rich in different types of fatty acids has different effects on obesity-related OA: SFA and n-6 PUFA have a certain pro-inflammatory effect and can accelerate the progress of OA;n-3 PUFA has a certain anti-inflammatory effect and can alleviate OA progresses;and MUFA may have anti-inflammatory effects.3.The TLR4/My D88/NF-κB signaling pathway is involved in the effects of different types of fatty acids on obesity-related OA.SFA,MUFA and n-6 PUFA activate the TLR4/My D88/NF-κB signaling pathway,while n-3 PUFA can inhibit Its activation. |
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