Study on the Effects of 8-O-acetyl-shanzhiside Methylester on the Expression of HDAC 1-5 in the Spinal Dorsal Horn of Rats with Chronic Inflammatory Pain and Its Relationship with JAK 2-STAT3 Signaling Pathway
- VernacularTitle:8-O-乙酰山栀子苷甲酸对慢性炎性痛模型大鼠脊髓背角内HDAC1～5表达的影响及与JAK2-STAT3信号通路的关系研究
- Author:
Jian WANG
1
,
2
;
Xiaoli XIAO
3
;
Jia CUI
1
;
Lei WANG
1
;
Tingting FAN
1
;
Wei ZHANG
1
Author Information
1. Dept. of Pharmacy，the First Affiliated Hospital of Air Force Military Medical University，Xi’an 710032，China
2. Dept. of Ambulatorium，No. 94750 Military Hospital of PLA，Fujian Liancheng 366200，China
3. Dept. of Rheumatology，the Affiliated TCM Hospital of Shanghai Universit y of TCM，Shanghai 200071，China
- Publication Type:Journal Article
- Keywords:
8-O-acetyl-safalinoside;
Chronic inflammatory pain;
Histone deacetylase;
Astrocytes;
JAK2-STAT3;
Rats
- From:
China Pharmacy
2019;30(5):608-613
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To study the effects of 8-O-acetyl-shanzhiside methylester （8-OaS） on the expression of histone deacetylase 1-5 （HDAC1-5） in the spinal dorsal horn of chronic inflammatory pain model rats， and its relationship with Janus-activated kinase 2-signal transductions and activators of transcription 3 （JAK2-STAT3） signaling pathway. METHODS： SD rats were randomly divided into normal control group， sham operation group （normal saline）， complete Freund’s adjuvant （CFA） group （normal saline）， 8-OaS low-dose， medium-dose and high-dose groups （2， 20， 200 μg/kg）， with 6 rats in each group. Except for normal control group and sham operation group， chronic inflammatory pain model was induced by subcutaneous injection of CFA into the left hind toe of rats in other groups； after modeling， those groups were given relevant medicine intraperitoneally， once a day， for consecutive 7 d. Thermal radiation method was used to detect the latency of paw withdraw in rats on the 1st， 2nd， 3rd， 4th， 5th， 6th， 7th， 8th， 11th and 15th day of administration. Rats were grouped and given medicine according to the above method of the latter 5 groups. The protein expression of HDAC 1-5， phosphorylated JAK2 （pJAK2） and phosphorylated STAT3 （pSTAT3） in the spinal dorsal horn of lumbar enlargement segment in rats were detected by Western blot method after last medication. Rats were randomly divided into sham operation group （normal saline）， CFA group （normal saline）， 8-OaS group （20 μg/kg） and JAK2-STAT3 inhibtor AG490 group （8 mg/kg）， with 6 rats in each group； IP model was established by same method as above and then were given relevant medicine intraperitoneally， once a day， for consecutive 7 d. The expression of HDAC5 and glial fibrillary acidic protein （GFAP） in spinal dorsal horn of rats were detected by immunofluorescence histochemical staining. RESULTS： Compared with normal control group and sham operation group， the latency of paw withdraw was shortened significantly in other groups （P＜0.05）. Compared with CFA group， the latency of paw withdraw was prolonged significantly in 8-OaS low-dose， medium-dose and high-dose groups （P＜0.05）， in dose-dependent manner. Compared with sham operation group， the protein expression of HDAC 1-5， pJAK2 and pSTAT3 in spinal dorsal horn of rats were increased significantly in CFA group （P＜0.05）. Compared with CFA group， the protein expression of HDAC5， pJAK2 and pSTAT3 in spinal dorsal horn of rats were decreased significantly in 8-OaS low-dose， medium-dose and high-dose groups （P＜0.05）， but there was no statistical significance in the protein expression of HDAC 1-4 （P＞0.05）. HDAC5 was expressed on astrocytes in the spinal dorsal horn； compared with sham operation group， the expression of GFAP and HDAC 5 were increased significantly in spinal dorsal horn of rats in CFA group （P＜0.05）. Compared with CFA group， the expression of GFAP and HDAC5 in spinal dorsal horn of rats were decreased significantly in 8-OaS group and AG490 group （P＜0.05）. CONCLUSIONS： 8-OaS can effectively relieve CFA-induced chronic inflammatory pain， the mechanism of which may be associated with the down-regulation of HDAC5 expression and the phosphorylation levels of JAK2 and STAT3.
