Mo Shu, Cui Yan, Sun Kehuan, Wang Haixia, Peng Xunqian, Ou Ling, Lei Xiaojun, Huang Mengtian, Mei Wenhui, Xin Ling, He Haibing, Peng Bojia, Tian Ya, Wang Panpan, Li Xiaoyun, Zhang Ronghua, Zhu Xiaofeng
The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, PR China; College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510630, PR China; Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong, 518000, PR China.
College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510630, PR China.
Ecotoxicol Environ Saf. 2021 Dec 1;225:112762. doi: 10.1016/j.ecoenv.2021.112762. Epub 2021 Sep 13.
A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1α-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1α-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demonstrated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.
高氯化钠（NaCl）饮食会影响肾功能损害并增加尿钙排泄，导致骨质流失。在肾小管中，钠氯共转运体（NCC）和氯离子通道5（CLC-5）参与调节尿钙排泄。此外，一些细胞因子，如骨形态发生蛋白7（BMP-7）和1α-羟化酶，由肾小管合成，作用于骨骼并在骨代谢中发挥重要作用。然而，NaCl与这些离子通道或细胞因子之间的具体机制仍需从多个方面进行研究。本研究在培养的正常大鼠肾小管上皮NRK-52E细胞中发现，高浓度的NaCl显著抑制细胞活力并增加细胞凋亡。高浓度的NaCl降低了骨密度（BMD），NCC和骨桥蛋白（OPN）的mRNA和蛋白质水平显著增加证明了这一点，但CLC-5、BMP-7和1α-羟化酶的水平降低。此外，我们发现去卵巢（OVX）大鼠高盐饮食12周后，肾皮质中这些指标的水平发生了变化。而且，这些大鼠第四和第五腰椎（LV4和5）以及股骨的骨密度显著降低，骨微结构遭到破坏。我们还证明，高浓度的NaCl通过调节离子通道NCC和CLC-5增强了对这些有利于增加骨密度的细胞因子的抑制作用。总之，我们的结果表明，高浓度的NaCl通过调节离子通道NCC和CLC-5降低骨密度。
