摘要
目的探讨异补骨脂素联合锌治疗对1型糖尿病大鼠骨强度和骨量的影响,并探索可能的机制。方法通过链脲佐菌素注射(60 mg/kg)建立了1型糖尿病大鼠模型;随后1型糖尿病大鼠随机分为1型糖尿病组(Con)、锌治疗组(Zn)、异补骨脂素组(Bgz)以及锌联合异补骨脂素组(Zn+Bgz),每组10只;其中异补骨脂素组和锌治疗组以及联合治疗组大鼠分别接受硫酸锌、异补骨脂素以及两者联合治疗12周;待治疗结束后使用Micro-CT、HE染色切片、骨生物力学检测以及蛋白质印迹观察治疗效果以及可能的机制。结果治疗12周后,与Zn组及Bgz组相比,Zn+Bgz组的大鼠骨小梁数量和骨密度得到明显改善。Zn+Bgz组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较Zn组及Bgz组明显改善(P<0.05)。治疗12周时,Zn+Bgz组最大负荷、刚度和最大功耗较Zn组及Bgz组显著增加,差异有统计学意义(P<0.05)。和Zn组及Bgz组比较,Zn+Bgz组的大鼠Wnt/β-catenin信号通路被激活,Wnt 1、Wnt 5a、p-GSK-3β、GSK-3β、β-catenin水平显著上调,差异有统计学差异(P<0.05)。结论异补骨脂素及锌均可以通过Wnt/β-catenin信号通路激活介导对1型糖尿病大鼠骨骼的保护作用,且联合治疗效果更佳。
Objective To investigate the effect of isopsoralen combined with zinc treatment on bone strength and bone mass in type 1 diabetic rats,and explore possible mechanisms.Methods In this study,type 1 diabetic rat models were established by streptozotocin injection(60 mg/kg);subsequently,type 1 diabetic rats were randomly divided into type 1 diabetic group(Con),zinc treatment group(Zn),and tonic The osteolipin group(Bgz)and zinc combined with isopsoralen group(Zn+Bgz),10 in each group;Among them,rats in the isopsoralen group and the zinc treatment group and the combination treatment group received zinc sulfate,Psoralen and the combination of the two were treated for 12 weeks;after treatment,Micro-CT,HE stained sections,bone biomechanical detection and Western blot were used to observe the treatment effect and possible mechanism.Results After 12 weeks of treatment,compared with the Zn group and the Bgz group,the number of trabeculae and bone density in the Zn+Bgz group were significantly improved.BMD,TV/BV,Tb.N,Tb.Th,and Tb.Sp in the Zn+Bgz group were significantly improved compared with the Zn and Bgz groups(P<0.05).At 12 weeks of treatment,the maximum load,stiffness,and maximum power consumption in the Zn+Bgz group were significantly increased compared with the Zn and Bgz groups(P<0.05),which was statistically significant(P<0.05).Compared with the Zn group and the Bgz group,the Wnt/β-catenin signaling pathway in the Zn+Bgz group was activated,and the levels of Wnt 1,Wnt 5a,p-GSK-3β,GSK-3β,andβ-catenin were significantly increased(P<0.05).Conclusion Both isopsoralen and zinc can activate the bone protection effect of type 1 diabetic rats through Wnt/β-catenin signaling pathway activation,and the combined treatment is better.
作者
常培学
李海波
方其超
许振培
符茂雄
CHANG Peixue;LI Haibo;FANG Qichao;XU Zhenpei;FU Maoxiong(Department of Geriatrics and Endocrinology, the Fourth People’s Hospital of Haikou, Haikou 571100, China;Department of Nephrology and Hemodialysis, Fourth People’s Hospital of Haikou, Haikou 571100, China;Department of Endocrinology, Second People’s Hospital Affiliated to Hainan Medical College, Haikou 570311, China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2020年第10期1470-1474,共5页
Chinese Journal of Osteoporosis
基金
海南省自然科学基金(817333)
海南省卫生计生行业科研项目(16A200071)。
关键词
锌
1型糖尿病
异补骨脂素
骨密度
大鼠
zinc
type 1 diabetes
isopsoralen
bone mineral density
rats