Berberine restored nitrergic and adrenergic function in mesenteric and iliac arteries from streptozotocin-induced diabetic rats
Berberine restored nitrergic and adrenergic function in mesenteric and iliac arteries from streptozotocin-induced diabetic rats
复制标题
小檗碱恢复链脲佐菌素诱导的糖尿病大鼠肠系膜和髂动脉的氮能和肾上腺素能功能
DOI：
10.1016/j.jep.2019.112140
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发表时间：
2019-11-15
影响因子：
5.4
通讯作者：
Zhao, Ding
中科院分区：
文献类型：
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作者：
Zhao, Lili;Liu, Shuai;Zhao, Ding
民族药理学相关性：据报告，血管周围神经病变涉及糖尿病相关血管疾病。黄连的干燥根茎。（拉丁名：甘草;通用名称：黄连是中医治疗糖尿病（消渴）的常用药物，现代临床和药理研究证实其对糖尿病周围神经病变具有良好的治疗作用。黄连素（BBR）是黄连治疗糖尿病的主要有效成分，据报道可改善糖尿病中枢和周围神经病变。本研究的目的：探讨BBR对糖尿病大鼠肠系膜动脉和髂动脉的氮能和肾上腺素能神经功能的影响。材料和方法：本研究将实验动物随机分为对照组、糖尿病组和糖尿病大鼠灌胃BBR组。采用腹腔注射链脲佐菌素（STZ，55 mg·kg ~（-1））建立糖尿病大鼠模型。造模后2周，BBR治疗组灌胃盐酸小檗碱（四川协力制药有限公司）。有限公司、Ltd; 200 mg.kg（-1）.day（-1））在蒸馏水中再稀释2周。切除上级肠系膜动脉和髂动脉。采用电场刺激法（EFS）诱导大鼠动脉收缩，观察糖尿病大鼠肠系膜上动脉（上级动脉）和髂动脉神经原性功能的变化，以及BBR对糖尿病大鼠早期神经血管功能障碍的影响。分别使用荧光测定和ELISA定量从氮能神经和肾上腺素能神经释放的一氧化氮（NO）和去甲肾上腺素（NA）。结果：EFS引起上级肠系膜动脉和髂动脉频率依赖性收缩反应，0.1 μ mol·L ~（-1）河豚毒素（TTX）可阻断这种收缩反应，或被1 μ mol·L ~（-1）酚妥拉明抑制或被0.1 mmol·L ~（-1）N-ω-硝基-L-精氨酸甲酯盐酸盐（L-NAME）增加。在上级肠系膜动脉，L-NAME对糖尿病大鼠肠系膜上动脉的收缩反应明显减弱，NO释放量减少，而髂动脉则无明显变化。糖尿病大鼠髂动脉对酚妥拉明的收缩反应增强，NA释放增加，而上级肠系膜上动脉则无此变化。结论：在STZ诱导的早期糖尿病大鼠中，肠系膜和髂动脉血管张力的神经控制发生了不同程度的改变。上级肠系膜动脉的氮能神经减少和髂动脉的肾上腺素能神经增强均有助于血管收缩反应的增强。BBR可逆转糖尿病大鼠的上述变化，提示BBR可能通过调节血管紧张性的神经平衡而发挥作用。
Ethnopharmacological relevance: Perivascular neuropathy was reported to involve in the vascular disorders associated with diabetes. The dried rhizomes of Coptis chinensis Franch. (Latin name: Coptidis Rhizoma; common name: Huang Lian in China), used frequently in Traditional Chinese medicine to treat diabetes (Xiaoke), have been confirmed to possess beneficial effects on diabetic peripheral neuropathy by modern clinical and pharmacological studies. Berberine (BBR), the main effective component of Huang Lian in the treatment of diabetes, is reported to ameliorate diabetic central and peripheral neuropathy. However, the effects of BBR on nerve function of mesenteric and iliac arteries are unclear.Aim of the study: To investigate the effects of BBR on the diabetes-induced changes in nitrergic and adrenergic function in mesenteric and iliac arteries.Materials and methods: In this study, the animals were randomized into three groups: control rats, diabetic rats, and diabetic rats gavaged with BBR. We established diabetic rat model using intraperitoneal injection of streptozotocin (STZ, 55 mg kg(-1)). Two weeks after model establishment, those in the BBR-treated groups were gavaged with berberine chloride (Sichuan Xieli Fharmaceutical. Co., Ltd; 200 mg.kg(-1).day(-1)) diluted in distilled water for another 2 weeks. The superior mesenteric artery and iliac artery were excised. Electric field stimulation (EFS) was used to induce arterial vasoconstriction and explore (1) the diabetes-induced changes in neurogenic function of the superior mesenteric artery and iliac artery; (2) the effects of BBR on neurovascular dysfunction in the early stage of STZ-induced diabetic rats. Nitric oxide (NO) and noradrenaline (NA) released from the nitrergic and adrenergic nerves were quantified using fluorescence assays and ELISA, respectively.Results: EFS induced frequency-dependent vasoconstrictions in both superior mesenteric and iliac artery, and the contractile responses of arteries were abolished by 0.1 mu mol.L-1 tetrodotoxin (TTX), or inhibited by 1 mu mol.L-1 phentolamine or increased by 0.1 mmol.L-1 N-omega-Nitro-L-arginine methyl ester hydrochloride (L-NAME). In superior mesenteric artery, but not in iliac artery, the changes of contractile responses with L-NAME were significantly decreased in diabetic rats, and NO release was less also. In contrast, in iliac artery of diabetic rats, but not in superior mesenteric artery, the changes of contractile responses with phentolamine were increased, and NA release was increased significantly. All these changes in diabetic rats on both superior mesenteric artery and iliac artery were reversed by treated with BBR.Conclusions: In the STZ-induced early diabetic rats, neural control of mesenteric and iliac vasomotor tone are altered differently. The diminished nitrergic nerve in superior mesenteric artery and enhanced adrenergic nerve in iliac artery both contributed to increased vasocontrictor responses. All these changes in diabetic rats were reversed by BBR, suggesting a novel mechanism of BBR in balance of neural regulation of vascular tone.