补骨脂煎剂对2型糖尿病大鼠骨折愈合过程中Wnt/PPARγ信号通路影响研究

摘要

目的:探讨补骨脂煎剂对2型糖尿病大鼠骨折愈合过程中Wnt/PPARγ信号通路的影响.方法:选取健康雄性SD大鼠72只,随机分为对照组、模型组、氟化钠组以及补骨脂组,各18只.对照组建立胫骨骨折模型,其余各组采用链脲佐菌素腹腔注射建立2型糖尿病胫骨骨折模型,并给予相应的药物治疗.对大鼠胫骨BMD、FPG及血清Ca、P、ALP水平、胫骨弯曲强度和扭矩、骨组织β-catenin、p-GSK3β、PPARγ蛋白表达水平进行检测.结果:治疗后,与模型组比较,各组大鼠胫骨BMD水平较高,且补骨脂组>氟化钠组(P<0.05);各组大鼠血清Ca、P水平较低,且补骨脂组<氟化钠组(P<0.05),各组大鼠血清ALP水平较高,且补骨脂组>氟化钠组(P<0.05);各组大鼠胫骨弯曲强度和扭矩水平较高,且补骨脂组>氟化钠组(P<0.05);各组大鼠骨组织β-catenin蛋白表达水平较高,且补骨脂组>氟化钠组(P<0.05),各组大鼠骨组织p-GSK3β蛋白表达水平较低,且补骨脂组<氟化钠组(P<0.05);各组大鼠骨组织PPARγ蛋白表达水平较低,且补骨脂组<氟化钠组(P<0.05).结论:补骨脂煎剂能够明显提高2型糖尿病骨折大鼠BMD、血清ALP水平,降低血清Ca、P水平,提高骨的生物力学强度,加速骨折愈合,可能与上调β-catenin蛋白表达,下调p-GSK3β、PPARγ蛋白表达,激活Wnt信号通路、抑制PPARγ信号通路有关.%Objective:To analysis the effect of Buguzhi Decoction on Wnt/PPARγ signal pathway in healing process of fracture in type 2 diabetic rats.Methods: Seventy-two healthy male SD rats were randomly divided into control group, model group, sodium fluoride and Buguzhi group, each with 18 rats.The tibial fracture model was established in control group, type 2 diabetic tibial fracture model were established by intraperitoneal injection of streptozotocin in the other groups, and were given corresponding drug treatment.The tibia BMD, FPG and serum Ca、P、ALP levels, tibia bending strength and torque, the expression levels of β-catenin, p-GSK3β and PPARγ in bone tissue were detected.Results: After treatment, compared with model control group, the tibia BMD levels were higher in rats of each group,and Buguzhi group was higher than sodium fluoride group(P<0.05);the serum Ca、P levels were lower in rats of each group,and Buguzhi group was lower than sodium fluoride group (P<0.05);the serum ALP levels were higher in rats of each group,and Buguzhi group was higher than sodium fluoride group (P<0.05);the tibia bending strength and torque levels were higher in rats of each group,and Buguzhi group was higher than sodium fluoride group (P<0.05);the expression of β-catenin protein in bone tissue of rats in each group was higher in rats of each group, and Buguzhi group was higher than sodium fluoride group (P<0.05);the expression of p-GSK3β protein in bone tissue of rats in each group was lower in rats of each group, and Buguzhi group was lower than sodium fluoride group (P<0.05);the expression of PPARγ protein in bone tissue of rats in each group was lower in rats of each group, and Buguzhi group was lower than sodium fluoride group (P<0.05).Conclusions: Buguzhi Decoction can effectively improve the BMD、serum ALP levels of fracture and type 2 diabetic rats, reduce serum Ca、P levels, improve the biomechanical strength of bone, accelerate fracture healing, it may be associated with up regulation ofβ-catenin protein expression, down regulation of p-GSK3β、PPARγ protein expression, activation of the Wnt signaling pathway and inhibition of the PPAR signaling pathway.