肾衰营养胶囊对肾性骨病模型大鼠肾功能和骨代谢的改善作用及其对BMP-7/Smads信号通路的影响

doi:10.13481/j.1671-587X.20240309

Abstract

Abstract:

Objective To discuss the improvement effect of Shenshuai Yingyang Capsule in the renal osteodystrophy model rats and its effect on the bone morphogenetic protein （BMP）-7/Smads signaling pathway，and to clarify the relationship between renal function and bone metabolism in the renal osteodystrophy model rats. Methods Fifty SPF SD rats were selected， and 10 of which were randomly chosen as control group， and the remaining 40 rats were used to establish the renal osteodystrophy model. Thirty successful modeling rats were divided into model group， positive control group， and Shenshuai Yingyang Capsule group， and there were 10 rats in various groups. The rats in control and model groups were given saline， the rats in positive control group were given 0.01 mg·kg^-1 calcitriol， and the rats in Shenshuai Yingyang Capsule group were given 1.2 g·kg^-1 Shenshuai Yingyang Capsule， all the rats were treated for 12 weeks. HE staining was used to observe the pathomorphology of femur tissue of the rats in various groups； automatic biochemical analyzer and chemiluminescence were used to detect the kidney function and calcium-phosphorus metabolism indicators in serum of the rats in various groups； real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in various groups； Western blotting method was used to detect the expression levels of BMP-7， phosphorylated BMP-7（p-BMP-7）， Smad1/5/8， and phosphorylated-Smad1/5/8 （p-Smad1/5/8） proteins in femur tissue of the rats in various groups. Results The HE staining results showed that there was normal trabecular arrangement in control group with unchanged osteoblasts and osteoid area. In model group， the trabecular width and average osteoid area were increased， while the number of osteoblasts was decreased. In positive control and Shenshuai Yingyang Capsule groups， the trabecular width and average osteoid area were decreased， and the number of osteoblasts was increased. Compared with control group，the levels of blood urea nitrogen （BUN） and serum creatinine （Scr） of the rats in model group were increased （P<0.05）； compared with model group， the levels of BUN and Scr of the rats in positive control and Shenshuai Yingyang Capsule groups were decreased （P<0.05）； compared with positive control group， the levels of BUN and Scr of the rats in Shenshuai Yingyang Capsule group were decreased （P<0.05）. Compared with control group， the level of calcium ion （Ca²⁺） in serum of the rats in model group was decreased（P<0.05）， and the levels of phosphorus ion （P^3-）， parathyroid hormone （PTH）， and alkaline phosphatase （ALP） were increased （P<0.05）； compared with model group， the levels of Ca²⁺ in serum of the rats in positive control and Shenshuai Yingyang Capsule groups were increased（P<0.05）， and the levels of P^3-， PTH， and ALP were decreased （P<0.05）； compared with positive control group， the level of Ca²⁺ in serum of the rats in Shenshuai Yingyang Capsule group was increased， and the levels of P^3-， PTH， and ALP were decreased （P<0.05）. The RT-qPCR results showed that compared with control group，the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in model group were decreased （P<0.05）； compared with model group， the expression levels of BMP-7 and Smad1/5/8 mRNA of the rats in positive control drug group and Shenshuai Yingyang Capsule group were increased （P<0.05）； compared with positive control group， the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in Shenshuai Yingyang Capsule group were increased （P<0.05）. The Western blotting results showed that compared with control group， the expression levels of BMP-7， p-BMP-7， Smad1/5/8， and p-Smad1/5/8 proteins in femur tissue of the rats in model group were decreased （P<0.05）； compared with model group， the expression levels of BMP-7， p-BMP-7， Smad1/5/8， and p-Smad1/5/8 proteins in femur tissue of the rats in positive control group and Shenshuai Yingyang Capsule group were increased （P<0.05）； compared with positive control group， the expression levels of BMP-7， p-BMP-7， Smad1/5/8， and p-Smad1/5/8 proteins in femur tissue of the rats in Shenshuai Yingyang Capsule group were increased （P<0.05）. Conclusion Shenshuai Yingyang Capsule can improve the kidney function and calcium-phosphorus metabolism disorders in the renal osteodystrophy model rats， promote the proliferation of the bone marrow stromal cells， and enhances the bone metabolism； its mechanism may be related to the activation of BMP-7/Smads signaling pathway.

Key words: Renal osteodystrophy, Shenshuai Yingyang Capsule, Bone morphogenetic protein-7, Recombinant mothers against decapentaplegic homolog, Bone density

CLC Number:

R692

Jiebin CHEN,Rong HU,Peijia LYU,Chengjie LI,Lianbo WEI. Improvement effect of Shenshuai Yingyang Capsule on renal function and bone metabolism in renal osteodystrophy model rats and its effect on BMP-7/Smads signaling pathway[J].Journal of Jilin University(Medicine Edition), 2024, 50(3): 658-665.

Figures/Tables 7

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References 21

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Group	BUN[c_B/(mmol·L^－1)]	Scr[c_B/(μmol·L^－1)]
Control	5.36±0.64	27.95±3.88
Model	17.28±2.53^*	171.25±25.03^*
Positive control	14.32±2.34^△	123.18±21.14^△
Shenshuai Yingyang Capsule	11.36±2.10^△#	68.36±7.54^△#

Group	Ca²⁺[c_B/(mmol·L^－1)]	P^3－[c_B/(mmol·L^－1)]	PTH[ρ_B/(ng·L^－1)]	ALP[λ_B/(U·L^－1)]
Control	2.35±0.35	1.15±0.20	1.42±0.23	36.52±4.33
Model	1.78±0.25^*	3.18±0.41^*	3.52±0.45^*	79.55±8.74^*
Positive control	1.94±0.29^△	2.61±0.34^△	2.44±0.34^△	61.02±7.18^△
Shenshuai Yingyang Capsule	2.28±0.33^△#	2.25±0.31^△#	1.85±0.32^△#	48.39±5.47^△#

Group	BMD（g·cm^－2）	Bone volume fraction（η/%）
Control	0.18±0.04	0.57±0.06
Model	0.11±0.01^*	0.31±0.03^*
Positive control	0.13±0.02^△	0.39±0.04^△
Shenshuai Yingyang Capsule	0.16±0.03^△#	0.48±0.05^△#

Group	BMP-7 mRNA	Smad1/5/8 mRNA
Control	1.00±0.01	1.00±0.01
Model	0.32±0.04^*	0.33±0.04^*
Positive control	0.51±0.06^△	0.68±0.07^△
Shenshuai Yingyang Capsule	0.84±0.09^△#	0.82±0.09^△#

Group	BMP-7 protein	p-BMP-7 protein	Smad1/5/8 protein	p-Smad1/5/8 protein
Control	1.00±0.01	1.00±0.01	1.00±0.01	1.00±0.01
Model	0.34±0.04^*	0.21±0.03^*	0.41±0.05^*	0.34±0.05^*
Positive control	0.55±0.06^△	0.45±0.05^△	0.63±0.07^△	0.65±0.07^△
Shenshuai Yingyang Capsule	0.79±0.08^△#	0.68±0.07^△#	0.85±0.09^△#	0.77±0.08^△#

Improvement effect of Shenshuai Yingyang Capsule on renal function and bone metabolism in renal osteodystrophy model rats and its effect on BMP-7/Smads signaling pathway

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