The Anti-oxidant Effect Of Huangqiguizhiwuwu Decoction On Paclitaxel Induced Peripheral Neuropathy

Objective To establish a rat model of paclitaxel-induced chronic peripheral neuropathy and observing the changes of pain behavior,the expression of SOD activity and MDA content in serum and spinal cord tissue; pathological morphological of dorsal root ganglion cells, the expression of TRPs (TRPV1, TRPA1) channel and NF-κB and MAPKs signaling pathway protein in dorsal root ganglion, to explore the preventive and treatment effect of Huangqiguizhiwuwu decoction on paclitaxel-induced peripheral neuropathy.Methods After adaptiving feed,40adult male SD rats were randomly divided into control group, model group,group of Huangqiguizhiwuwu low-dose and Huangqiguizhiwuwu high-dose (n=10).Model group, high-dose group and low-dose group received intraperitoneal administration2mg/kg paclitaxel solution on0,2,4,6days, blank group received intraperitoneal administration with the same volume of EL. Meanwhile, control group and model group were received2ml of0.9%NS by gastric lavage daily, the Chinese medicine high-group was treated with Huangqiguizhiwuwu decoction at the does of10ml/kg (2.48g/ml)daily, the Chinese medicine low-group was treated with Huangqiguizhiwuwu decoction at the does of10ml/kg (0.62g/ml)daily. On the day when paclitaxel was injected, chinese medicine was given one hour before paclitaxel administration. The rats were observed the response to drugs. Measurement of von Frey test and acetone test were required once a week. On21day, L4-L5bilateral dorsal root ganglia and spinal cord tissue were collected and blood sample was taken from abdominal aorta.1, Detect the level of SOD activity and MDA content in serum and spinal cord tissue after administration of paclitaxel and Huangqiguizhiwuwu decoction, respectively.2,Through Nissl staining to observe pathology of rat dorsal root ganglion and measure the nucleolar size.3, Detect the gene expression changes of TRPA1and TRPV1in the dorsal root ganglion by qRT-PCR.3, Detect the protein expression changes of of NF-κB and MAPKs in the dorsal root ganglion by Western-blot.Results The success of CIPN rat model preparation was proved by the behavior measurement and histological examination. Compared with control group, model group’s mechanical allodynia and cryalgesia obviously decrease(p<0.01). Huangqiguizhiwuwu decoction can alleviate paclitaxel-induced hyperalgesia(p<0.01), and Huangqiguizhiwuwu high-dose is better(p<0.05). Von Frey4g、8g、15g show that comparing with control group, model group’s percentage of mechanical allodynia obviously increase (P<0.01). The detection of SOD activity and MDA content in serum and spinal cord tissue show that administration of paclitaxel can dramaticly reduce the level of SOD activity in serum and spinal cord tissue (P<0.01) and incease MDA content in serum and spinal cord tissue (P<0.01). There is a positive correlation between SOD level and the severity of hyperalgesia. Compared with control group, nucleolar size significantly increase after the injection of paclitaxel (p<0.01), while administration of Huangqiguizhiwuwu decoction can reverse this increase (p<0.01). PCR results show that comparing with control group, paclitaxel can induce TRPV1、TRPA1mRNA expression increased in dorsal root ganglion (P<0.01).Compared with model group, the Chinese medicine can down-regulate the expression of TRPV1、TRPA1mRNA (P<0.01). Western-blot results show that there was no statistical difference between the groups(P>0.05).Conclusions Huangqiguizhiwuwu decoction can alleviate paclitaxel induced neuropathy simultaneously upregulate the level of SOD activity in serum and spinal cord tissue and incease MDA content in serum and spinal cord tissue, inducing TRPV1、TRPA1mRNA expression increased in dorsal root ganglion.But may not interfere the NF-κBand MAPKs Signaling pathway.