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目的观察盐酸川芎嗪对原发性痛经大鼠血液及组织中VEGF及其受体的影响。方法 40只SD大鼠,随机分为正常对照组、模型组、盐酸川芎嗪注射液组(20 mg/kg,ip),田七痛经胶囊组(2.0 g/kg,ig,阳性药对照组)。采用皮下注射己烯雌酚建立原发性痛经大鼠模型,给药结束后,除模型组灌胃给予等体积蒸馏水外,各给药组连续给药28 d。末次给药45 min后,每组大鼠腹腔注射缩宫素0.2 U,观察各组大鼠40 min内扭体次数和扭体反应发生率;给予缩宫素1.5 h后,将各组大鼠麻醉致死,取血4 mL,制备血清,采用酶联免疫吸附实验测定血清中血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、一氧化氮(NO)和超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)含量以及血浆中6-酮前列腺素F1a(6-keto-prostaglandin F1a,6-keto-PGF1a)含量,采用Western blot方法检测子宫组织中VEGFR-2蛋白表达情况。结果与模型组相比,盐酸川芎嗪注射液组能显著减少痛经大鼠的扭体次数(P<0.05)。酶联免疫吸附实验结果表明,盐酸川芎嗪注射液组可显著减少血清中VEGF和hs-CRP的含量,增加NO的含量,同时增加血浆中6-keto-PGF1a的含量(P<0.05)。Western blot结果表明:与模型组相比,盐酸川芎嗪注射液组可显著降低VEGFR-2蛋白表达(P<0.05)。结论盐酸川芎嗪注射液对原发性大鼠模型具有良好的镇痛作用,该作用机制与其减少血清中VEGF和hs-CRP的含量,增加NO的含量,升高血浆中6-keto-PGF1a的含量及降低VEGFR-2蛋白表达相关,为治疗原发性痛经性疾病提供了新的临床理论依据。
Objective To observe the effect of ligustrazine hydrochloride on VEGF and its receptor in the blood and tissues of rats with primary dysmenorrhea. Methods 40 SD rats were randomly divided into normal control group, model group, ligustrazine hydrochloride injection group (20 mg / kg ip), Tianqi Tongjing capsule group (2.0 g / kg, ig, positive drug control group) . The model of primary dysmenorrhea was established by subcutaneous injection of diethylstilbestrol. After the administration, rats in the model group were administered with equal volume of distilled water by gavage, and each administration group was given continuous administration for 28 days. At 45 minutes after the last administration, each group of rats were injected intraperitoneally with 0.2 U of oxytocin to observe the number of writhing reactions and the rate of writhing reaction within 40 minutes in each group. After 1.5 hours of oxytocin administration, rats in each group The mice were killed by anesthesia and 4 mL of blood was taken for preparation of serum. The levels of serum vascular endothelial growth factor (VEGF), nitric oxide (NO) and hypersensitive C-reactive protein were measured by enzyme linked immunosorbent assay (ELISA) reactive protein (hs-CRP) and the content of 6-keto-prostaglandin F1a (6-keto-PGF1a) in the uterus were detected by Western blot. Results Compared with the model group, ligustrazine hydrochloride injection group can significantly reduce the number of writhing in dysmenorrhea rats (P <0.05). The results of enzyme-linked immunosorbent assay showed that Ligustrazine Hydrochloride injection significantly reduced the content of VEGF and hs-CRP, increased the content of NO and increased the content of 6-keto-PGF1a in plasma (P <0.05). Western blot results showed that compared with model group, Ligustrazine hydrochloride injection group could significantly decrease VEGFR-2 protein expression (P <0.05). Conclusion Tetramethylpyrazine hydrochloride injection has good analgesic effect on primary rat model, which is related to the decrease of serum VEGF and hs-CRP content, increase of NO content and increase of 6-keto-PGF1a in plasma Content and reduce the expression of VEGFR-2 protein, provide a new clinical theory for the treatment of primary dysmenorrhea disease.