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Effects and potential mechanism of action of Shujin Huoxue Decoction on symptoms and nucleus pulposus inflammation in rats with lumbar disc herniation

LI Xiang;QIU Zhi-he;XIE Wei-yong;HUANG Gang;MIN Shui-ping;WANG An-sen;Department of Orthopedics,Shenzhen Longgang District Orthopedic Hospital;Department of Rehabilitation,Shenzhen Longgang District Orthopedic Hospital;  
Objective To analyze the effects of Shujin Huoxue Decoction on symptoms and nucleus pulposus inflammation in rats with lumbar disc herniation(LDH), and to explore its possible mechanism of action based on phospholipase A_2(PLA_2) activity and cyclooxygenase 2(COX2)/prostaglandin E_2(PGE_2) pathway. Methods Among 95 male SD rats, 15 rats were randomly selected as control group, and the remaining rats were applied into the modeling of LDH. Seventy-five successful LDH rat models were randomly divided into model group, indomethacin group, and low-, moderate-and high-dose Shujin Huoxue Decoction groups, with 15 rats in each group. The indomethacin group was given indomethacin(7.5 mg/kg) by gavage. The low-, moderate-and high-dose Shujin Huoxue Decoction groups were intragastrically given 9.54 g/kg, 19.08 g/kg, and 38.16 g/kg of Shujin Huoxue Decoction by gavage, respectively. The control and model groups were given the same amount of normal saline by gavage. After the end of the last administration, rats′ general status was observed. On the 7 th, 14 th and 28 th day after the modeling, the activity of PLA_2 in nucleus pulposus tissues was measured; twenty-eight days after the modeling, rats′ nerve root tissues at the L_5-L_6 spinous process were obtained to detect the mRNAs and proteins expression levels of PLA_2, COX2, PGE_2, tumor necrosis factor α(TNF-α), and interleukin 1β(IL-1β). Results Compared with the control group, rats in the model group had reduced activity, obvious claudication, or concomitant abnormal contralateral toes and other symptoms, exhibiting increased activity of PLA_2 in nucleus pulposus tissues at each time point and elevated mRNAs and proteins expression levels of PLA_2, COX2, PGE_2, TNF-α, and IL-1β in nerve root tissues(all P0.05). Compared with the model group, the indomethacin group and the low-, moderate-and high-dose Shujin Huoxue Decoction groups exhibited symptom remission, basically normal gait, gradually recovered diet, and decreased activity of PLA_2 in nucleus pulposus tissues at each time point(all P0.05); moreover, rats in the indomethacin group and the moderate-and high-dose Shujin Huoxue Decoction groups yielded lower mRNAs and proteins expression levels of PLA_2, COX2, PGE_2, TNF-α, and IL-1β in nerve root tissues(all P0.05). There was no statistically significant difference between the indomethacin group and the high-dose Shujin Huoxue Decoction group in the activity of PLA_2 in nucleus pulposus tissues, or in the mRNA and protein expression level of PLA_2, COX2, PGE_2, TNF-α, or IL-1β in nerve root tissues(all P0.05).Conclusion Shujin Huoxue Decoction at a high dose(38.16 g/kg) can reduce nucleus pulposus inflammation in LDH rats by inhibiting the activity of PLA_2 in the nucleus pulposus and the expression of COX2/PGE_2 pathway, thus ameliorating the symptoms of LDH, which could serve as a potential drug for LDH treatment.
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