Pejman Laleh, Omrani Hasan, Mirzamohammadi Zahra, Keyhanmanesh Rana
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Basic Med Sci. 2014 Dec;17(12):1012-9.
For determining the mechanism of anti-asthmatic effect of thymoquinone, this investigation evaluated the effect of thymoquinone in the presence of selective A2A and A2B adenosine receptor antagonists (ZM241385 and MRS1706, respectively).
Seventy guinea pigs were randomly divided to 7 groups; control (C), sensitized with ovalbumin (S), sensitized groups pretreated with thymoquinone (S+TQ), ZM241385 (S+Anta A2A), MRS1706 (S+Anta A2B), thymoquinone and antagonists (S+Anta A2A+TQ and S+Anta A2B+TQ). Thymoquinone and each of these antagonists with 3 mg/kg dose were injected i.p. on 10(th) day of sensitization protocol. Tracheal responsiveness (TR) to methacholine and ovalbumin (OA), and total and differential cell count in lung lavage fluid (LLF) in different groups were measured.
Increased EC50 and LLF neutrophil count and decreased TR to methacholine and OA, LLF eosinophil and basophil counts were observed in S+TQ group compared to S group (P<0.001 to P<0.05). Significant decrease in EC50 (P<0.01), LLF neutrophil, lymphocyte and monocyte count (P<0.001 for all) and significant increase in TR to OA (P<0.01), LLF total WBC (P<0.01) and eosinophil count (P<0.001) were observed in S+A2A group compared to S+TQ group. There was significant increase in LLF eosinophil and monocyte counts in S+Anta A2B group compared with S+TQ group (P<0.001 for both). In S+TQ+Anta A2A group, there was significant increase in LLF eosinophil (P<0.001) and significant decrease in LLF neutrophil (P<0.01) and monocyte (P<0.001) counts compared with S+TQ group.
Thymoquinone affects adenosine receptors, which suggest that some of its anti-inflammatory effects may be mediated by these receptors.
为确定黑种草醌的抗哮喘作用机制,本研究评估了在存在选择性A2A和A2B腺苷受体拮抗剂(分别为ZM241385和MRS1706)的情况下黑种草醌的作用。
70只豚鼠随机分为7组;对照组(C)、卵清蛋白致敏组(S)、用黑种草醌预处理的致敏组(S + TQ)、ZM241385组(S + Anta A2A)、MRS1706组(S + Anta A2B)、黑种草醌与拮抗剂联合组(S + Anta A2A + TQ和S + Anta A2B + TQ)。在致敏方案的第10天,腹腔注射剂量为3 mg/kg的黑种草醌及上述每种拮抗剂。测量不同组对乙酰甲胆碱和卵清蛋白(OA)的气管反应性(TR),以及肺灌洗液(LLF)中的细胞总数和分类计数。
与S组相比,S + TQ组的半数有效浓度(EC50)升高,LLF中性粒细胞计数增加,对乙酰甲胆碱和OA的TR降低,LLF嗜酸性粒细胞和嗜碱性粒细胞计数减少(P < 0.001至P < 0.05)。与S + TQ组相比,S + A2A组的EC50显著降低(P < 0.01),LLF中性粒细胞、淋巴细胞和单核细胞计数显著减少(均P < 0.001),对OA的TR显著增加(P < 0.01),LLF白细胞总数(P < 0.0!)和嗜酸性粒细胞计数(P < 0.001)增加。与S + TQ组相比,S + Anta A2B组的LLF嗜酸性粒细胞和单核细胞计数显著增加(均P < 0.001)。与S + TQ组相比,S + TQ + Anta A2A组的LLF嗜酸性粒细胞显著增加(P < 0.001),LLF中性粒细胞(P < 0.01)和单核细胞(P < 0.001)计数显著减少。
黑种草醌影响腺苷受体,这表明其某些抗炎作用可能由这些受体介导。