首页|基于PI3K/Akt/NF-κB信号通路探讨滋阴补肾方对糖尿病合并去卵巢骨质疏松大鼠骨代谢的影响

基于PI3K/Akt/NF-κB信号通路探讨滋阴补肾方对糖尿病合并去卵巢骨质疏松大鼠骨代谢的影响

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目的 基于磷脂酰肌醇-3-激酶/蛋白激酶B/核因子κB(PI3K/Akt/NF-κB)信号通路探究滋阴补肾方对糖尿病合并去卵巢骨质疏松大鼠骨代谢的影响.方法 将60 只SPF级雌性大鼠随机分为对照组、模型组、骨化三醇组及滋阴补肾方高、中、低剂量组,每组10 只.除对照组外,其余组大鼠均摘除双侧卵巢、喂食高糖高脂饲料并注射链脲佐菌素建立糖尿病合并去卵巢骨质疏松模型.造模成功后,滋阴补肾方高、中、低剂量组分别按照干药剂量20 g/kg、10 g/kg、5 g/kg灌胃滋阴补肾方药液,骨化三醇组灌胃0.1 μg/kg骨化三醇,对照组和模型组灌胃等量生理盐水,均1次/d,连续8 周.末次灌胃结束后,股动脉取血,自动生化分析仪测定空腹血糖(FPG)、钙、磷、三酰甘油(TG)、胆固醇(TC)水平;腹主动脉取血,ELISA法测定糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);RT-PCR法检测骨组织中PI3K、Akt、NF-κB mRNA相对表达量.结果 与对照组比较,模型组FPG、HbA1c、HOMA-IR、TG、TC水平及骨组织中NF-κB mRNA相对表达量均明显升高(P均<0.05),FINS、血钙、血磷水平及骨组织中PI3K mRNA、Akt mRNA相对表达量均明显降低(P均<0.05);与模型组比较,骨化三醇组和滋阴补肾方各组FPG、HbA1c、HOMA-IR、TG、TC水平及骨组织中NF-κB mRNA相对表达量均明显降低(P均<0.05),FINS、血钙、血磷水平及骨组织中PI3K mRNA、Akt mRNA相对表达量均明显升高(P均<0.05),且滋阴补肾方高剂量组各指标改善情况均明显优于滋阴补肾方低剂量组(P均<0.05).结论 滋阴补肾方可通过介导PI3K/Akt/NF-κB信号通路改善糖尿病合并去卵巢骨质疏松大鼠的骨代谢,同时可调节糖代谢,减轻胰岛素抵抗.
Decoction for nourishing Yin and invigorating kidney improves bone metabolism of diabetic rats complicated with ovariectomized osteoporosis through PI3K/Akt/NF-κB signaling pathway
Objective It is to explore the effects of decoction for nourishing Yin and invigorating kidney on bone metab-olism in diabetic rats complicating with ovariectomized osteoporosis rats through phosphatidyl inositol 3-kinase/protein ki-nase B/nuclear factor-kappaB(PI3K/Akt/NF-κB)signaling pathway.Methods Sixty SPF-grade female rats were randomly divided into control group,model group,calcitriol group,and high,medium,and low dose groups of decoction for nouris-hing Yin and invigorating kidney,with 10 rats in each group.The rats in all groups except for the control group were trea-ted with bilateral oophorectomy,fed with high-sugar and high-fat diets,and were injected with streptozotocin to establish models of diabetes mellitus complicating with ovariectomized osteoporosis.After successful modeling,the high,medium and low dose groups of decoction for nourishing Yin and invigorating kidney were given 20 g/kg,10 g/kg and 5 g/kg of med-icated solution of decoction for nourishing Yin and invigorating kidney,respectively,the calcitriol group was given0.1 μg/kg of calcitriol by gavage,and the control group and model group were given an equal volume of normal saline,all once daily,continuously treated for 8 weeks.At the end of drug administration,the blood was collected from femoral artery to deter-mine the levels of fasting plasma glucose(FPG),calcium,phosphorus,triacylglycerol(TG),and cholesterol(TC)by automatic biochemical analyzer,the blood was collected from abdominal aorta to determine the levels of glycated hemoglobin(HbA1c)and fasting insulin(FINS)by ELISA,and the insulin resistance index(HOMA-IR)was calculated;the relative expressions of PI3K,Akt,and NF-κB mRNAs in bone tissues were detected by RT-PCR.Results Compared with the con-trol group,the levels of FPG,HbA1c,HOMA-IR,TG,TC and the relative expression of NF-κB mRNA in bone tissues were significantly increased in the model group(all P<0.05),and the levels of FINS,blood calcium,blood phosphorus and the relative expressions of PI3K mRNA and Akt mRNA in bone tissues were significantly decreased(all P<0.05).Compared with the model group,the levels of FPG,HbA1c,HOMA-IR,TG,TC and the relative expression of NF-κB mRNA in bone tissues were significantly decreased in the calcitriol group and each groups of decoction for nourishing Yin and invigorating kidney(all P<0.05),and the levels of FINS,blood calcium,blood phosphorus and the relative expres-sions of PI3K mRNA and Akt mRNA in bone tissues were significantly increased(all P<0.05),and the improvement of every index in the high dose groups of decoction for nourishing Yin and invigorating kidney was significantly better than that in the low dose group(all P<0.05).Conclusion Decoction for nourishing Yin and invigorating kidney can improve bone metabolism as well as regulate sugar metabolism and relieve insulin resistance through mediating the PI3K/AKT/NF-κB sig-naling pathway in diabetic rats complicating with ovariectomized osteoporosis.

diabetes mellitusosteoporosis decoction for nourishing Yin and invigorating kidneyPI3K/Akt/NF-κB signaling pathways

王鸿艳、孙勤国、黄威、杨倩、罗蒙、吕琨

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湖北中医药大学第一临床学院,湖北 武汉 430065

武汉大学同仁医院(武汉市第三医院),湖北 武汉 430060

糖尿病 骨质疏松 滋阴补肾方 PI3K/Akt/NF-κB信号通路

湖北省卫生健康委联合基金

WJ2019H414

2024

现代中西医结合杂志
中国中西医结合学会河北分会,中华中医药学会

现代中西医结合杂志

CSTPCD
影响因子:1.775
ISSN:1008-8849
年,卷(期):2024.33(7)
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