| Objective:In this experiment,high fat induced obesity mice and db/db mice were used as research objects.After intervention with celestrol,the effects of celestrol on body weight and glucose metabolism in mice were investigated.By detecting the activity of oxidase in plasma and renal tissue and expression levels of Keapl,Nrf2 and PGC-1α genes and proteins in kidney,to further explore the preliminary mechanism of celestrol in ameliorating renal injury and alleviating oxidative stress response.Methods:Twenty-four healthy male C57BL/6 mice aged 7-8 weeks and 10 healthy male db/db mice aged 10-11 weeks were selected.Before the experiment,all mice were housed and fed in separate cages in a suitable environment with free access to pure water.After 1 week,the 24 C57BL/6 mice were divided into three groups according to the randomization principle:normal control group(NC group),model control group(OC group)and CelA group,with 8 mice in each group(n=8).Mice in NC group were fed with low-fat diet,while mice in OC and CelA groups were fed with high-fat diet for 12 weeks,during which body weight and fasting blood glucose were dynamically monitored to confirm the success of the establishment of the obesity mouse model.Ten db/db mice were randomly divided into two groups:control group(DC group)and CelB group,with five mice in each group(n=5),both fed on high-fat chow.CelA group and CelB group were treated by intraperitoneal injection of celastrol 100ug/kg/d for 21 days,and the other three groups were intraperitoneal injection of the same volume of normal saline.During the administration period,the body weight of mice in each group was recorded separately according to the experimental protocol,and the fasting blood glucose of the mice was measured using a blood glucose meter to complete the glucose tolerance and insulin tolerance test in each group.Immediately after the experiment,blood was collected from the orbit and kidney tissues.ELISA was performed to detect SOD activity,MDA content,GSH-Px activity and CAT activity in the plasma and kidney tissues of mice;western blot and Real-time PCR were used to detect the expression levels of Keap1,Nrf2 and PGC-1α related pathways in the kidney of mice.Results:(1)Compared with OC group,after 3 weeks of treatment,body weight and food intake of CelA group were significantly decreased(P<0.05),fasting blood glucose was significantly decreased(P<0.05),glucose tolerance and insulin tolerance were significantly increased(P<0.05),and the area under the curve of glucose tolerance and insulin tolerance was significantly decreased(P<0.05).The levels of SOD,GSH-Px and CAT activities in plasma and kidney tissues of mice in the CelA group were significantly increased(P<0.05)and MDA was significantly decreased(P<0.05)compared with the OC group.Compared with the OC group,the levels of Nrf2 and PGC-1α genes and protein in the kidneys of the CelA mice were significantly increased(P<0.05)and the levels of Keapl genes and protein were significantly decreased(P<0.05).(2)Compared to the DC group,mice in the CelB group showed a significant decrease in body weight,food intake and fasting blood glucose(P<0.05),.and a significant increase in glucose tolerance and.insulin tolerance(P<0.05)after the drug intervention.SOD,GSH-Px and CAT levels in plasma and renal tissues were significantly increased(P<0.05)and MDA levels were significantly decreased(P<0.05)in the intervention group.Renal Nrf2 and PGC-1α gene and protein levels were significantly higher(P<0.05)and Keapl gene and protein levels were significantly lower(P<0.05)compared to the DC group.Conclusion:Celastrol can reduce body weight,improve glucose metabolism and insulin resistance,and promote glucose homeostasis in high-fat diet-induced obesity and db/db mice;and through the detection of oxidative stress indicators and molecular levels,it was found that Celastrol may achieve anti-oxidative stress effects through regulating the Keap1/Nrf2/PGC-1α signaling pathway,thereby reducing kidney damage. |
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