ABSTRACT
Aim To explore the internal mechanism of NK2 activation of NK cells from the perspective of "mitochondrial dysfunction-abnormal cell activation".Methods NK-92MI cells were divided into blank group, TSLP group, 1, 5, and 10 μmol·L-1 Mdivi-1 dose groups.The levels of IL-4, IL-5, and IFN-γ in the supernatant of each group were determined by ELISA; The expression of p-Drp1 and MnSOD protein in each group was determined by Western blotting; the ROS level of each group was detected by DHE staining and flow cytometry; mitochondrial morphology was observed by confocal laser in each group of cells.Results ELISA showed that compared with control group, the levels of IL-4 and IL-5 in cell supernatant of TSLP group significantly increased, and the level of IFN-γ was down-regulated(P<0.05); Compared with TSLP group, the levels of IL-4 and IL-5 in cell supernatant of 5 and 10 μmol·L-1 Mdivi-1 group decreased, and the IFN-γ concentration of the 10 μmol·L-1 Mdivi-1 group rose(P<0.05).DHE staining and flow cytometry showed that ROS level of cells in TSLP group was significantly higher than control group.Compared with TSLP group, ROS level of the 5 and 10 μmol·L-1 Mdivi-1 groups decreased(P<0.05).The laser confocal results showed that after TSLP stimulation, a large number of spherical mitochondria were formed in cells.This phenomenon was improved to a certain extent after the intervention of 5, 10 μmol·L-1 Mdivi-1.Western blot analysis showed that the p-Drp1 level of NK-92MI cells in TSLP group was significantly up-regulated, and the expression of MnSOD decreased, while the intervention of Mdivi-1 effectively reversed the changes in the expression of the above-mentioned molecules.Conclusions Mitochondrial dynamic imbalance may be one of the internal mechanisms of abnormal activation of NK cells, and it may be an important target for regulating NK2 activation of NK cells and improving the allergic inflammatory response mediated by it.
ABSTRACT
Astragali Radix (AR) is one of the most famous drugs for enhancing Qi in Chinese herbal medicines, and shows satisfactory medicinal value. Recently, AR has made significant progress in research of central nervous system (CNS) injury and neurodegeneration. AR and its active ingredients have satisfactory effects on modulation of nerve inflammation, inhibition of apoptosis, enhancement of vascular repair and neuroregeneration. The mechanism may be related to the regulation of microscopic Qi mitochondrial function and the recovery of cell metabolic disorders. In this article, we systematically discuss the pharmacological effects and possible mechanisms of AR from the perspective of the core pathological changes, and evaluate its drug safety through combing of the related toxicology researches to provide a reference for application of AR in CNS disease treatments.