Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase
Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase
复制标题
乌药提取物对糖尿病晚期失代偿期膀胱功能障碍小鼠模型的影响
DOI：
10.1186/s12906-019-2448-1
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发表时间：
2019-02-04
影响因子：
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通讯作者：
Cao, Hongying
中科院分区：
文献类型：
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作者：
Yang, Xufeng;Lian, Dawei;Cao, Hongying
本研究旨在探讨乌药提取物对糖尿病小鼠膀胱功能障碍(DBD)模型的影响及其作用机制。方法雄性C57BL/6J小鼠喂饲高脂饲料4周后，腹腔注射链脲佐菌素(STZ)。通过持续12周的高血糖建立DBD小鼠模型(失代偿期后期)，然后给予RL提取物治疗4周。服药期间，每周进行一次空腹血糖(FBG)检测。4周后进行口服葡萄糖耐量试验(OGTT)、纸片空斑试验(VSOP)和尿动力学检查。我们还进行了苏木精-伊红(H&E)染色和Masson‘s三色染色，以观察膀胱的组织学。然后，测定对，-亚甲基三磷酸腺苷、辣椒素、氯化钾和氨基甲胆碱的收缩反应。结果糖尿病组小鼠的空腹血糖、糖化血红蛋白和尿量明显增加，RL治疗后无明显变化。尿动力学试验显示，DBD组小鼠的最大膀胱容量(MBC)、残余容量(RV)和膀胱顺应性(BC)显著增加，排尿效率(VE)和尿量(MV)显著降低。与模型组比较，RL治疗组尿动力学指标明显改善，MBC、RV、BC降低，VE、MV升高。膀胱壁厚度和肌胶原比值明显增加，RL可有效减轻病理改变。DBD小鼠的膀胱条对刺激的反应也降低，RL治疗显著增加收缩。此外，糖尿病小鼠膀胱中M-3受体和TRPV1的基因表达水平下调，而RL治疗可恢复这些基因的表达水平。结论RL提取物可改善失代偿期糖尿病小鼠的膀胱排尿功能，其机制可能与调节膀胱中M-3受体和TRPV1的基因表达有关，而不是改善血糖水平。
BackgroundThis study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase.MethodsMale C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4weeks. During administration, the fasting blood glucose (FBG) test was performed once a week. Four weeks later, oral glucose tolerance test (OGTT), voided stain on paper (VSOP), and urodynamic alteration were explored. We also performed haematoxylin and eosin (H&E) and Masson's trichrome staining to observe the histology of the bladder. Then, the contractile responses to , -methylene ATP, capsaicin (CAP), KCl and carbachol were measured. Moreover, qPCR assay was performed to analyse the bladder gene expression levels of M-3 receptors and TRPV1.ResultsThe diabetic mice exhibited higher FBG, OGTT and urine production, and no substantial alteration was observed after RL treatment. Urodynamic test showed the maximum bladder capacity (MBC), residual volume (RV) and bladder compliance (BC), as well as the decrement of voided efficiency (VE) and micturition volume (MV), remarkably increased in the DBD mice. Furthermore, RL treatment significant improved urodynamic urination, with lower MBC, RV, and, BC, as well as higher VE and MV, as compared with the model groups. The wall thickness of the bladder and the ratio of smooth muscle/collagen remarkably increased, and RL could effectively attenuate the pathological change. The response of bladder strips to the stimulus was also reduced in the DBD mice, and RL treatment markedly increased the contraction. Furthermore, the gene expression levels of M-3 receptors and TRPV1 were down-regulated in the bladders of the diabetic mice, whereas RL treatment retrieved those gene expression levels.ConclusionsRL extracts can improve the bladder voiding functions of the DBD model mice in later decompensated phase, and underlying mechanisms was associated with mediating the gene expression of M-3 receptors and TRPV1 in the bladder instead of improving blood sugar levels.