School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, PR China.
J Ethnopharmacol. 2013 Dec 12;150(3):1128-36. doi: 10.1016/j.jep.2013.10.039. Epub 2013 Oct 30.
ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes. MATERIALS AND METHODS: The detrusor muscle strips were isolated from urinary bladders of streptozotocin-induced diabetic rats, 5% sucrose-induced diuretic rats or normal rats, and were placed in organ bath. The contractions induced by electrical field stimulation (EFS), carbachol, KCl, adenosine triphosphate, and the effects of berberine on those contractions were measured. RESULTS: The EFS- or KCl-induced contraction of detrusor muscle was significantly decreased in diabetic rats as compared with diuretic or normal rats. Atropine and suramin inhibited EFS-induced contraction. In diabetic rats, the atropine sensitive components were decreased in EFS-induced contraction of detrusor muscle, and the adenosine triphosphate-induced contraction was significantly increased. The carbachol-induced contrations were not different among groups. Berberine significantly potentiated EFS-induced contractions of detrusor muscle both from normal and diabetic rats, but the potentiated effect of BBR was more sensitive to atropine in diabetic rats. Berberine also potentiated adenosine triphosphate-induced contraction of detrusor muscle, but did not change carbachol- or KCl-induced contraction. CONCLUSION: The neurogenic contraction of urinary bladder detrusor muscle is decreased while purinergic contraction of bladder detrusor muscle is increased in rats with early stage diabetes. Berberine increases the neurogenic contractile response to EFS possibly via both presynaptic increasing neurotransmitters release and postsynaptic potentiation of purinergic transmitter-regulated response in rat urinary bladder detrusor; and in diabetic rats, berberine increases neurogenic contractile response mainly via the presynaptic increasing acetylcholine release.
民族药理学相关性：在中国，黄连已被用于治疗糖尿病超过 1400 年。小檗碱是黄连的主要生物碱之一，是黄连降血糖的主要成分。本研究旨在探讨小檗碱对早期糖尿病大鼠膀胱逼尿肌神经原性收缩功能障碍的作用。
材料与方法：从链脲佐菌素诱导的糖尿病大鼠、5%蔗糖诱导的利尿大鼠或正常大鼠的膀胱中分离逼尿肌肌条，置于器官浴中。测量电刺激（EFS）、卡巴胆碱、氯化钾、三磷酸腺苷诱导的收缩以及小檗碱对这些收缩的影响。
结果：与利尿或正常大鼠相比，糖尿病大鼠的 EFS 或氯化钾诱导的逼尿肌收缩明显降低。阿托品和苏拉明抑制 EFS 诱导的收缩。在糖尿病大鼠中，EFS 诱导的逼尿肌收缩的阿托品敏感成分减少，三磷酸腺苷诱导的收缩明显增加。各组间卡巴胆碱诱导的收缩无差异。小檗碱显著增强正常和糖尿病大鼠逼尿肌的 EFS 诱导收缩，但在糖尿病大鼠中，BBR 的增强作用对阿托品更为敏感。小檗碱还增强三磷酸腺苷诱导的逼尿肌收缩，但不改变卡巴胆碱或氯化钾诱导的收缩。
结论：早期糖尿病大鼠膀胱逼尿肌的神经原性收缩减少，而膀胱逼尿肌的嘌呤能收缩增加。小檗碱通过增加神经递质释放和增强嘌呤能递质调节的后突触反应，增加 EFS 诱导的神经原性收缩反应，可能在大鼠膀胱逼尿肌中增加神经原性收缩反应；在糖尿病大鼠中，小檗碱通过增加乙酰胆碱释放主要增加神经原性收缩反应。
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