Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression

Enhui LU; Qingshu LI; Yun TAN

doi:10.16016/j.2097-0927.202205134

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Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression

Basic Medicine | 更新时间：2026-01-09

- Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression
- Journal of Army Medical University Vol. 44, Issue 23, Pages: 2421-2428(2022)
- 作者机构：
  
  1.401336 重庆，重庆市东南医院骨科
  2.400010 重庆，重庆医科大学基础医学院病理科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202205134
  CLC： R341;R363.22;R681.53
- Received：24 May 2022，
  
  Revised：2022-08-10，
  
  Published：15 December 2022
- 稿件说明：
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Enhui LU, Qingshu LI, Yun TAN. Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression[J]. Journal of Army Medical University, 2022, 44(23): 2421-2428.
DOI：

Enhui LU, Qingshu LI, Yun TAN. Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression[J]. Journal of Army Medical University, 2022, 44(23): 2421-2428. DOI： 10.16016/j.2097-0927.202205134.

摘要

目的

探讨人源性激肽释放酶结合蛋白(kallistatin，KS)对椎间盘髓核细胞的作用及可能机制。

方法

在正常和退变髓核中检测KS的表达；过氧化氢/KS处理细胞后分为Control、H

、KS及H

+KS 4组，检测各组细胞凋亡和细胞外基质(extracellular matrix，ECM)的变化；利用沉默信息调节因子2相关酶Ⅰ(silencing information regulator 2 related enzyme Ⅰ，SIRT1)小干扰RNA (siRNA-SIRT1)/KS处理细胞后分为Control、H

、KS+H

+siRNA-NC及KS+H

+siRNA-SIRT1 5组，检测各组髓核细胞凋亡及ECM的表达。

结果

退变椎间盘髓核中KS的mRNA和蛋白的表达水平明显低于正常髓核(

＜0.05)；相比于H

组，KS组及H

+KS组髓核细胞凋亡率明显降低(

＜0.05)，凋亡基因Caspase3、Caspase9和Bax mRNA及蛋白表达量明显降低(

＜0.05)，抗凋亡基因Bcl2表达量明显增加(

＜0.05)；GAG含量、Collagen Ⅱ和Aggrecan表达显著提高(

＜0.05)。当siRNA-SIRT1敲降髓核细胞SIRT1表达后，相比于Control、KS+H

和KS+H

+siRNA-NC组，KS+H

+siRNA-SIRT1组凋亡率显著增加，GAG含量、Collagen Ⅱ和Aggrecan蛋白表达也显著降低(

＜0.05)。

结论

KS可通过诱导SIRT1表达抑制H

诱导的人髓核细胞凋亡和ECM降解。

Abstract

Objective

To investigate the effect of human tissue kallikrein-binding protein

kallistatin (KS) on intervertebral disc nucleus pulposus cells and the possible mechanism.

Methods

The expression of KS was detected in normal and degenerative nucleus pulposus cells isolated from the patients undergoing

thoracolumbar surgery due to thoracolumbar fracture and lumbar disc herniation in our hospital from April 2020 to August 2021. The cells were divided into Control group

group

KS group and H

+KS group. The changes of cell apoptosis and extracellular matrix (ECM) in each group were detected. After treatment of silencing information regulator 2 related enzyme Ⅰ (SIRT1) small interfering RNA/KS treatment

the cells were divided into control group

group

KS+H

group

KS+H

+siRNA-NC group and KS+H

+siRNA-SIRT1 group. Cell apoptosis and ECM of the nucleus pulposus cells in each group were detected.

Results

The mRNA and protein levels of KS were significantly lower in the nucleus pulposus cells isolated from the degenerative intervertebral disc than the normal nucleus pulposus cells (

0.05). Compared with the H

group

the apoptotic rate was obviously decreased (

0.05)

the mRNA and protein levels of apoptosis-related genes Caspase3

Caspase9 and Bax were notably decreased (

0.05)

the expression of anti-apoptotic gene Bcl2 was remarkably increased

and the content of GAG and the expression levels of Collagen Ⅱ and Aggrecan were statistically increased (

0.05) in the KS group and H

+KS group (

0.05). When the expression of SIRT1 was knocked down by siRNA-SIRT1 in the nucleus pulposus cells

the KS+H

+SIRT1 group had significantly increased apoptotic rate

and decreased content of GAG and protein levels of Collagen Ⅱ and Aggrecan when compared with the control group

KS+H

group

and KS+H

+siRNA-NC group (

0.05).

Conclusion

KS inhibits H

-induced apoptosis and ECM degradation of human nucleus pulposus cells by inducing SIRT1 expression.

关键词

Keywords

references

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