| Objective:To study the inhibitory effect of a new type of intestinal insulinotropic analog DAla2GIP on inflammatory response in osteoarthritis model rats.Methods:Twenty-four 3-month-old male SD rats were purchased from the Experimental Animal Center of Shanxi Medical University and divided into a sham operation group,a model group,a DAla2GIP treatment group,and a DAla2GIP+GIP?3-30?NH2 treatment group according to the random number table method.Each group have 6 rats.Except for the rats in the sham operation group,which only cut the switch capsule,the other experimental rats need to cut the anterior cruciate ligament and remove the medial meniscus.Eight weeks after the rat knee OA model was established,the DAla2GIP treatment group was injected intraperitoneally with DAla2GIP?25nmol/kg?,and the DAla2GIP+GIP?3-30?NH2?GIP receptor antagonist?treatment group was intraperitoneally injected with DAla2GIP?25nmol/kg?and GIP?3-30?NH2?25nmol/kg?.The sham operation group and the model group were intraperitoneally injected with the same volume of normal saline,twice a week for 8 weeks.Fourteen weeks after modeling,all experimental animals were trained in the walkway for two weeks.16weeks after modeling,the experimental animals were sacrificed and gross specimens were scored,safranin O-solid green staining,and the contents of IL-1?and IL-18 in synovial fluid were measured.Results:?1?Chronic treatment with DAla2GIP relieves gait abnormalities caused by OA cartilage tissue damage:relative to the sham operation group?normal step ratio:?98.04%±1.96%?,average speed through the runway:??21.33±2.59?cm/s?,the maximum contact area of the right hind limb:??0.67±0.03?cm2?,the maximum contact area of the left hind limb:??0.61±0.07?cm2?,the distance between the hind paws:??4.18±0.23?cm??,the normal step ratio?82.33%±6.60%?,average speed through the runway?13.93±2.51?cm/s),maximum contact area of right hind limb??0.67±0.03?cm2?,maximum contact area of left hind limb??0.61±0.07?cm2?),hind paw spacing??3.14±0.48?cm?)of the model group are significantly reduced?all P<0.01?;while the normal step ratio??94.55%±5.45%??,the average time to pass the runway??19.07±2.46?cm/s?,the maximum contact area of the right hind limb??0.58±0.05?cm2?,the maximum contact area of the left hind limb??0.60±0.09?cm2?,the distance between the hind paws??3.77±0.27?cm?of DAla2GIP treatment group were significantly higher than the model group?all P<0.05?and the DAla2GIP+GIP?3-30?NH2 treatment group?normal step ratio:?80.25%±4.57%?,average speed through the runway:??12.48±2.71?cm/s?,maximum contact area of right hind limb:??0.39±0.05?cm2?,maximum contact area of left hind limb:??0.42±0.06?cm2?,hind paw spacing:??3.05±0.33?cm?,all P<0.01?.Compared with the distance between the front paws of SD rats in the sham operation group??4.03±0.11?cm?,the distance between the front paws of the model group was significantly shortened??2.73±0.33?cm,P<0.0001?;and the distance between the front paws of the DAla2GIP treatment group??3.77±0.27?cm?was higher than the model group and DAla2GIP+GIP?3-30?NH2??2.73±0.27?cm?,but it was not statistically significant?P>0.05?.?2?DAla2GIP chronic treatment attenuates OA cartilage tissue damage:In the sham operation group,the cartilage was not damaged,the surface was smooth,and the color was bright and flexible.However,the knee joint surface cartilage defect in the model group and the DAla2GIP+GIP?3-30?NH2 treatment group was severe,the elasticity was poor,a large number of osteophytes were generated,and the color was dim.Compared with the model group,the DAla2GIP treatment group had better cartilage color,and there was no exposed bone,but some small cartilage cracks were visible.Compared with the ICRS score of the sham operation group?15.33±0.82?,the ICRS score of the model group was significantly reduced??4.83±0.75?,P<0.0001?);while the ICRS score of the DAla2GIP treatment group?11.33±0.82?was significantly higher than the model group?P<0.0001?and DAla2GIP+GIP?3-30?NH2??5.00±1.27?,P<0.0001?.?3?Saffron O-solid green staining:The sham operation group and the DAla2GIP treatment group had the deepest staining of saffron O,normal cartilage thickness,and regular arrangement of chondrocytes,which indirectly reflected that the content of proteoglycan in the cartilage matrix was higher in these two groups.In the model group and the DAla2GIP+GIP?3-30?NH2 treatment group,the cartilage layer was lightly colored,unevenly stained,the cartilage layer was thin,and the chondrocytes were arranged randomly.?4?ELISA to determine the content of IL-1?,IL-18 in synovial fluid:Compared with the content of IL-1?in the knee joint fluid of the sham operation group??410±37.14?pg/ml?,the content of IL-1?in the model group was significantly increased??796.95±64.17?pg/ml,P<0.01?.The content of IL-1???435.65±27.07?pg/ml?in the DAla2GIP treatment group was significantly lower than that in the model group?P<0.01?and DAla2GIP+GIP?3-30?NH2??749.52±43.13?pg/ml,P<0.01?.Compared with the content of IL-18 in knee joint fluid of the sham operation group??214.64±28.02?pg/ml?,the content of IL-18 in the model group was significantly increased??372.92±45.93?pg/ml,P<0.01?.The content of IL-18??243.84±29.02?pg/ml?in the DAla2GIP treatment group was significantly lower than that in the model group?P<0.01?and DAla2GIP+GIP?3-30?NH2??344.25±36.20?pg/ml?,P<0.01).Conclusion:After chronic treatment with DAla2GIP,it inhibits the secretion of IL-1?and IL-18 in the synovial fluid of OA model rats,improves the gait of OA rats,and finally repairs the cartilage tissue damage of OA rats. |
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