Aggravation of spinal cord injury by TGF-beta via activating NF-kappa B

作者:Xu Haibo; Zhang Yong; Wang Xinzhi; Shen Yimin; Li Liubing; Dong Qirong*; Zhong Qinjian*
来源:International Journal of Clinical and Experimental Pathology, 2016, 9(10): 10810-10816.

摘要

The incidence of spinal cord injury (SCI) is gradually increased by years. Nuclear factor kappa B (NF-kappa B) has multiple biological activities including regulating inflammatory response, oxidative stress and further participating in SCI pathogenesis and progression. Transforming growth factor beta (TGF-beta) plays a role in inflammation and tissue repair. Its role and mechanism if SCI, however, have not been illustrated. Wistar rats were randomly divided into control group, SCI group which was prepared by improved ALLEN's weight-drop method, and TGF-beta group, which received tail vein injection of TGF-beta anti-sense oligonucleotide TGF-beta total phosphoric acid AODN. Basso, Beattie Bresnahan (BBB) locomotor rating scale was compared, plus SCI sensory function Reuter score. Real-time PCR and Western blot were used to detect TGF-beta and NF-kappa B expression. Caspase 3 activity was further measured, with TNF-alpha and IL-2 levels measured by ELISA. Compared to control group, SCI group had enhanced mRNA and protein expressions of NF-kappa B and TGF-beta, lower BBB score, higher Reuter score, higher caspase 3 activity, and more secretion of TNF-alpha and IL-2 (P<0.05). TGF-beta treatment significantly depressed NF-kappa B and TGF-beta expression, increased BBB score, lowered Reuter score, inhibited caspase 3 activity, and decreased TNF-alpha and IL-2 secretion (P<0.05 compared to SCI group). SCI group had elevated TGF-beta expression, further activating NF-kappa B and facilitating inflammation, enhancing apoptosis and aggravating SCI. Using TGF-beta as the target inhibited NF-kappa B expression, suppressing inflammation and inhibiting apoptosis, thus alleviating SCI.