Inhibitory effect of dipeptide peptidase inhibitors analogues on LPS-induced inflammatory response on microglia
10.11659/jjssx.11E016032
- VernacularTitle:二肽基肽酶抑制剂类似物对LPS诱导的小胶质细胞炎症反应的抑制作用
- Author:
Yingjun LIU
;
Song WANG
;
Hailin LIU
;
Chunqiao ZHOU
;
Hongmei PENG
;
Jun WEN
;
Yu CHEN
;
Dongmei HUANG
;
Zhiguo FAN
- Keywords:
dipeptide peptidase inhibitors analogues;
microglia;
lipopolysaccharide;
TLR-4;
NF-κB
- From:
Journal of Regional Anatomy and Operative Surgery
2017;26(1):13-17
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the inhibitory effect and mechanism of dipeptide peptidase inhibitors analogues on LPS -induced inflam-matory response on microglia .Methods Microglia cells were cultured ,isolated and purified from the neonatal Sprague-Dawley rats.Divided them into blank group ,negative control ,LPS group and medicine group ( parallel determination for 3 times each group ) after pharmacological preconditioning for 48 hours.The optimal concentration of microglia proliferation induced by LPS were measured by MTT assay .Observed the role of dipeptide peptidase inhibitors analogues on LPS-induced microglia in different concentrations .The interleukin1β( IL-1β) ,tumor necro-sis factor alpha ( TNF-α) were assayed by enzyme-linked immunorrbent assay ( ELISA ) .The expression of TLR-4 was detected by Western blotting and the expression of NF-κB was detected by RT-PCR.Results LPS induced the proliferation of microglia and significantly in-creased the release of inflammatory cytokines in LPS-stimulated primary microglia .Compared with the blank group ,dipeptide peptidase inhibi-tors analogues could inhibit this effect and the IC 50 values was 1.014 ×10 -2 mol/L to MG after pretreatment for 48 hours.Dipeptide peptidase inhibitors analogues could inhibit the release of TNF-αand IL-1 significantly(P<0.01),and it decreased the expression of TLR4 and NF-κB signif-icantly(P<0.01).Conclusion This research suggests that dipeptide peptidase inhibitors analogues restrain cell proliferation and inflammatory re-sponse of LPS-stimulated microglia,and the possible mechanism may be related to the inhibition of the expression of TLR-4 and NF-κB.