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
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篇名: 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
TITLE: Study on Mechanism of Analgesic Effect of 8-O-acetyl-safalinoside on Chronic Inflammatory Pain Model Rats
摘要: 目的:研究8-O-乙酰山栀子苷甲酸(8-OaS)对慢性炎性痛模型大鼠的镇痛作用机制。方法:将30只雄性SD大鼠分为假手术组(生理盐水)、模型组(生理盐水)和8-OaS低、中、高剂量组(3、10、30μg/kg),每组6只。除假手术组外,其余各组大鼠足底注射弗氏完全佐剂复制慢性炎性痛模型。造模成功后,各组大鼠鞘内给予相应药物,每天1次,连续给药7d后,采用Von-Frey细丝检测各组大鼠足底疼痛阈值,计算各组大鼠疼痛阈值曲线下面积和8-OaS的半数有效剂量(ED50)。另取36只雄性SD大鼠分为假手术组(生理盐水)、模型组(生理盐水)和8-OaS组(给药剂量为ED50),同法造模及给药,然后采用免疫荧光组织染色法观察各组大鼠脊髓背角内离子钙结合衔接分子1(Iba-1)、磷酸化p38丝裂原激活的蛋白激酶(p-p38MAPK)的阳性表达情况,采用Westernblotting法检测各组大鼠脊髓背角内Iba-1、p-p38MAPK、白细胞介素1β(IL-1β)、IL-6及肿瘤坏死因子α(TNF-α)的蛋白表达水平。结果:与假手术组比较,模型组大鼠足底疼痛阈值和曲线下面积均显著降低(P<0.01);与模型组比较,8-OaS低剂量组大鼠给药5、6、7d后足底疼痛阈值显著升高(P<0.05),8-OaS中、高剂量组大鼠足底疼痛阈值和曲线下面积均显著升高(P<0.05或P<0.01);8-OaS各剂量组上述指标大部分有显著差异(P<0.05或P<0.01);8-OaS的ED50为18.87μg/kg。免疫荧光组织染色和Westernblotting法结果显示,p-p38MAPK主要表达在Iba-1阳性表达的细胞上;与假手术组比较,模型组大鼠脊髓背角内Iba-1、p-p38MAPK的荧光密度和Iba-1、p-p38MAPK、IL-6、IL-1β、TNF-α蛋白表达水平均显著升高(P<0.05或P<0.01);与模型组比较,8-OaS组大鼠脊髓背角内Iba-1、p-p38MAPK的荧光密度和Iba-1、p-p38MAPK、IL-6、IL-1β、TNF-α蛋白表达水平均显著降低(P<0.05)。结论:鞘内给予8-OaS可有效缓解大鼠慢性炎性痛,其机制可能与抑制p38MAPK的磷酸化和IL-6、IL-1β、TNF-α的表达有关。
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.
期刊: 2020年第31卷第13期
作者: 张维,王健,范博渊,李梦颖,樊婷婷,李锐莉,程艳
AUTHORS: ZHANG Wei,WANG Jian,FAN Boyuan ,LI Mengying ,FAN Tingting ,LI Ruili,CHENG Yan
关键字: 8-O-乙酰山栀子苷甲酸;脊髓背角;p38丝裂原激活的蛋白激酶;炎性痛;大鼠;机制
KEYWORDS: 8-O-acetyl-safalinoside;Spinal dorsal horn ;p38 mitogen-activated protein kinase ;Inflammatory pain ;Rat;
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