Effects of dihydroxylphenyl lactic acid on inflammatory responses in spinal cord injury.
The initial mechanical tissue disruption of spinal cord injury (SCI) is followed by a period of secondary injury that increases the size of the lesion. Secondary injuries are associated with edema, inflammation, excessive cytokine release, excitotoxicity and cell apoptosis. 3,4-dihydroxyphenyl lactic acid (DLA) is one of the major water-soluble components of chemical constituents from Salvia miltiorrhiza (SM). To investigate the inhibition effects of DLA on secondary injury of SCI, focusing especially on suppression of inflammatory responses and the mechanism of this effect, the following studies were performed: Basso, Beattie, and Bresnahan (BBB) scores to assess motor functions till 10 days after SCI; Nissl and Fast Blue histological staining and immunohistochemistry of inhibitory-kappa B-alpha (IκB-α) and nuclear factor-kappa B (NF-κB) p65 subunit protein; levels of myeloperoxidase (MPO) activity analysis as an indicator of polymorphonuclear infiltration; IL-6 production in plasma 10 days after SCI; Western blot analysis to determine cytoplasm levels of IκB-α and NF-κB p65 subunit proteins in the nuclear fractions 10 days after SCI. DLA significantly attenuated the motor function and tissue damage following SCI in rats, significant reduced polymorphonuclear cell infiltration and IL-6 production, as well as reduced cytoplasm IκB-α degradation and the nuclear translocation of NF-κB p65 subunit protein after SCI. In conclusion, the results clearly demonstrate that DLA inhibit the inflammation responses induced by SCI via inhibiting effect of production of IL-6 and nuclear translocation of NF-κB.
Orthopaedic Department, Peking University Third Hospital, Beijing, China.
Xin
X
Chen
Changman
C
Zhou
Jun
J
Guo
Kai
K
Sun
Na
N
Zhao
Jiying
J
Yang
Yu
Y
Sun
Xiaoguang
X
Liu
Toshifumi
T
Hibi
Zhongjun
Z
Liu
Jingyan
J
Han
D015102:3,4-Dihydroxyphenylacetic Acid / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009186:Myelin Sheath / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D016328:NF-kappa B; D015102:3,4-Dihydroxyphenylacetic Acid; D009195:Peroxidase; D051550:I-kappa B Kinase