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Study on Mechanism of Analgesic Effect of 8-O-acetyl-safalinoside on Chronic Inflammatory Pain Model
Rats
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ZHANG Wei ，WANG Jian ，FAN Boyuan ，LI Mengying ，FAN Tingting ，LI Ruili ，CHENG Yan（1. Dept. of
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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）
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-1 β ，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 ED50 of 8-OaS was 18.87 μ g/kg. Results of
immunohistochemistry staining and Western blotting showed that p-p38 MAPK was mainly expressed in Iba-1 positive cells.
Compared with sham operation group，the fluorescence density of Iba-1 and p-p38 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-p38 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 p38 MAPK and the expression of IL-6，IL-1β and TNF-α.
KEYWORDS 8-O-acetyl-safalinoside；Spinal dorsal horn；p38 mitogen-activated protein kinase；Inflammatory pain；Rat；
Mechanism

炎性痛是临床疾病的常见并发症，如慢性胰腺炎、 d表达增加，表明小胶质细胞被激活，进而增加如白细胞
腰椎间盘突出症及慢性炎性损伤均可诱发炎性痛 [1-2] 。 介素 1β（IL-1β）、IL-6 及肿瘤坏死因子α（TNF-α）等炎症
近年来，随着人们生活节奏加快和生活习惯改变，慢性 介质的产生，促进脊髓背角内星形胶质细胞的活化，加
[5]
病发生率逐年升高，伴随而来的慢性炎性痛的发生率也 重脊髓背角内的炎症反应 。8-O-乙酰山栀子苷甲酸
[3]
逐渐升高，严重影响患者的生活质量和精神状态 。当 （8-OaS）是从中药独一味中提取的单体成分，相关研究
前对于慢性炎性痛的发生机制尚不明确，临床上治疗以 表明，其可通过抑制星形胶质细胞内TNF-α/细胞外调节
药物镇痛为主、物理手段为辅的方式，但药物的副作用 蛋白激酶（ERK）信号通路的活化并特异性降低组蛋白
较大，如吗啡类镇痛药物具有成瘾性 ，故对于慢性炎性 去乙酰化酶5的表达，从而发挥镇痛作用 [6-7] 。另有研究
[4]
痛发生机制的探索和治疗药物的更新显得尤为关键。 表明，p38丝裂原激活的蛋白激酶（p38 MAPK）的磷酸化
[8]
小胶质细胞是中枢神经系统内的巨噬细胞，离子钙 主要发生于脊髓背角小胶质细胞内 ，且在慢性炎性痛
结合衔接分子 1（Iba-1）是其特异性标记分子，相关研究 的发展窗口期会伴随小胶质细胞的激活而表达增加。
表明，在 L5 脊神经结扎模型大鼠体内，Iba-1 约在术后 3 基于此，本研究采用皮下注射弗氏完全佐剂复制大鼠慢

·1584 · China Pharmacy 2020 Vol. 31 No. 13 中国药房 2020年第31卷第13期