Study on Mechanism of Analgesic Effect of 8-O-acetyl-safalinoside on Chronic Inflammatory Pain Model Rats
- VernacularTitle:8-O-乙酰山栀子苷甲酸对慢性炎性痛模型大鼠的镇痛作用机制研究
- Author:
Wei ZHANG
1
;
Jian WANG
2
;
Boyuan FAN
3
;
Mengying LI
4
;
Tingting FAN
1
;
Ruili LI
1
;
Yan CHENG
5
Author Information
1. Dept. of Pharmacy，the First Affiliated Hospital of Air Force Military Medical University，Xi’an 710032，China
2. Outpatient Clinic，No. 94750 Army Hospital of PLA，Fujian Liancheng 366200，China
3. Dept. of Cardiology，Second Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710004，China
4. Dept. of Endocrinology and Metabolism，the First Affiliated Hospital of Air Force Military Medical University，Xi’an 710032，China
5. Outpatient Department，No. 94816 People’s Liberation Army，Fuzhou 350002，China
- Publication Type:Journal Article
- Keywords:
8-O-acetyl-safalinoside;
Spinal dorsal horn;
p38 mitogen-activated protein kinase;
Inflammatory pain;
Rat
- From:
China Pharmacy
2020;31(13):1583-1588
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To study the mechanism of analgesic effect of 8-O-acetyl-safalinoside （8-OaS） on chronic inflammatory pain model rats. METHODS ：Totally 30 male SD rats were divided into sham operation group （normal saline ）， model group （normal saline ），8-OaS low-dose ，medium-dose and high-dose groups （3，10，30 μg/kg），with 6 rats in each group. Except for sham operation group ，other groups were given planter injection of Freund ’s complete adjuvant to induce chronic inflammatory pain model. After successful modeling ，the rats in each group were given corresponding drugs intrathecally ，once a day，for 7 consecutive days. Then Von-Frey filaments were used to detect the planter pain threshold of the rats in each group ；the area under the planter pain threshold curve of each group and the half effective dose （ED50）of 8-OaS were calculated. Another 36 male SD rats were divided into sham operation group （normal saline ），model group （normal saline ）and 8-OaS group （dose of ED50），and the modeling method and administration route were the same as above. Immunofluorescence histochemical staining was used to observe the positive expression of ionized calcium binding adapter molecule 1（Iba-1）and signal molecule phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）；Western blotting assay was used to determine the expression of Iba- 1，p-p38 MAPK，IL-1β，IL-6 and TNF-α in spinal dorsal horn of rats. RESULTS：Compared with sham operation group ，plantar pain threshold and area under the curve in model group were reduced significantly （P＜0.01）. Compared with model group ，plantar pain threshold increased significantly after 5，6，7 days of administration in 8-OaS low-dose group （P＜0.05），plantar pain threshold and area under the curve in 8-OaS medium-dose and high-dose groups were increased significantly （P＜0.05 or P＜0.01）. Most of above indexes in each dose group of 8-OaS were signifficantly different ，and ED 50 of 8-OaS was 18.87 μ g/kg. Results of immunohistochemistry staining and Western blotting showed that p-p 38 MAPK was mainly expressed in Iba- 1 positive cells. Compared with sham operation group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba-1，p-p38 MAPK，IL-6，IL-1β and TNF-α were significantly increased in model group（P＜0.05 or P＜0.01）. Compared with model group ，the fluorescence density of Iba- 1 and p-p 38 MAPK in spinal dorsal horn ，the expression of Iba- 1，p-p38 MAPK， IL-6，IL-1β and TNF-α were decreased significantly in 8-OaS group （P＜0.05）. CONCLUSIONS ：Intrathecal administration of 8-OaS can effectively alleviate chronic inflammatory pain in rats. The mechanism may be related to the inhibition of the phosphorylation of p 38 MAPK and the expression of IL- 6，IL-1β and TNF-α.
