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Kallistatin诱导SIRT1表达抑制人髓核细胞凋亡及细胞外基质降解
Kallistatin inhibits apoptosis and extracellular matrix degradation of human nucleus pulposus cells by inducing SIRT1 expression
- 陆军军医大学学报 2022年44卷第23期 页码：2421-2428
- 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：
[谭云，E-mail: tanyun168@163.com TAN Yun, E-mail: tanyun168@163.com
- 基金信息：
DOI：10.16016/j.2097-0927.202205134
中图分类号： R341;R363.22;R681.53收稿：2022-05-24，
修回：2022-08-10，
纸质出版：2022-12-15
- 稿件说明：
移动端阅览
陆恩辉, 李庆姝, 谭云. Kallistatin诱导SIRT1表达抑制人髓核细胞凋亡及细胞外基质降解[J]. 陆军军医大学学报, 2022,44(23):2421-2428.
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.
陆恩辉, 李庆姝, 谭云. Kallistatin诱导SIRT1表达抑制人髓核细胞凋亡及细胞外基质降解[J]. 陆军军医大学学报, 2022,44(23):2421-2428. DOI： 10.16016/j.2097-0927.202205134.
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
2
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
2
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
2
O
2
、KS及H
2
O
2
+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
2
O
2
、KS+H
2
O
2
、KS+H
2
O
2
+siRNA-NC及KS+H
2
O
2
+siRNA-SIRT1 5组，检测各组髓核细胞凋亡及ECM的表达。
结果
2
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(
P
＜0.05)；相比于H
2
O
2
组，KS组及H
2
O
2
+KS组髓核细胞凋亡率明显降低(
P
＜0.05)，凋亡基因Caspase3、Caspase9和Bax mRNA及蛋白表达量明显降低(
P
＜0.05)，抗凋亡基因Bcl2表达量明显增加(
P
＜0.05)；GAG含量、Collagen Ⅱ和Aggrecan表达显著提高(
P
＜0.05)。当siRNA-SIRT1敲降髓核细胞SIRT1表达后，相比于Control、KS+H
2
O
2
和KS+H
2
O
2
+siRNA-NC组，KS+H
2
O
2
+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(
P
＜0.05)。
结论
2
KS可通过诱导SIRT1表达抑制H
2
O
2
诱导的人髓核细胞凋亡和ECM降解。
Abstract
Objective
2
To investigate the effect of human tissue kallikrein-binding protein
kallistatin (KS) on intervertebral disc nucleus pulposus cells and the possible mechanism.
Methods
2
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
H
2
O
2
group
KS group and H
2
O
2
+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
H
2
O
2
group
KS+H
2
O
2
group
KS+H
2
O
2
+siRNA-NC group and KS+H
2
O
2
+siRNA-SIRT1 group. Cell apoptosis and ECM of the nucleus pulposus cells in each group were detected.
Results
2
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 (
P
<
0.05). Compared with the H
2
O
2
group
the apoptotic rate was obviously decreased (
P
<
0.05)
the mRNA and protein levels of apoptosis-related genes Caspase3
Caspase9 and Bax were notably decreased (
P
<
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 (
P
<
0.05) in the KS group and H
2
O
2
+KS group (
P
<
0.05). When the expression of SIRT1 was knocked down by siRNA-SIRT1 in the nucleus pulposus cells
the KS+H
2
O
2
+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
2
O
2
group
and KS+H
2
O
2
+siRNA-NC group (
P
<
0.05).
Conclusion
2
KS inhibits H
2
O
2
-induced apoptosis and ECM degradation of human nucleus pulposus cells by inducing SIRT1 expression.
关键词
Keywords
references
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