6-羟多巴胺诱导帕金森病大鼠结肠中TRPV4和TRPM8通道表达的变化

V. Stetska, T. Dovbynchuk, N. Dziubenko, A. Zholos, G. Tolstanova
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引用次数: 1

摘要

帕金森病(PD)是一种神经退行性疾病,主要表现为黑质多巴胺能神经元的变性。非运动症状,特别是胃肠道紊乱,在20-80%的PD患者中可以在临床诊断PD的15-20年前观察到,这是PD发病机制中最重要的特征。瞬时受体电位(transient receptor potential, TRP)通道在整个胃肠道中表达,在味觉、体温调节、疼痛、粘膜功能和体内平衡、间质运动控制等方面发挥重要作用。本研究旨在探讨TRPV4和TRPM8通道在注射12 μg 6-羟多巴胺(6-OHDA)诱导的PD大鼠结肠GI运动功能中的作用。实验于PD诱导后第4周和第7个月进行,将大鼠随机分为:1组——假损伤大鼠,注射4 μl 0.9% NaCl, 4周后解剖(n = 5);II组:6-OHDA- pd大鼠,注射6-OHDA 4 μl 12 μg,注射后4周解剖(n = 5);III组:假损伤大鼠,4 μl 0.9% NaCl,注射7个月后尸检(n = 4);IV组- 6-OHDA- pd大鼠,注射4 μl 12 μg 6-OHDA,注射7个月后尸检(n = 5)。测定大鼠体重、GI转运时间、盲肠重量指数、酪氨酸羟化酶(TH)阳性细胞免疫组化鉴定及大鼠结肠TRPV4、TRPM8表达。我们发现,在实验的第七个月,GI穿越时间随着时间的推移翻了一番;6-OHDA大鼠盲肠重量指数提高57%;6-OHDA-PD大鼠结肠th阳性细胞数量减少2倍,而PD大鼠结肠TRPM8离子通道下调,TRPV4离子通道上调。综上所述,TRPV4和TRPM8离子通道可能是PD病理进展中的药理靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Changes in the expression of TRPV4 and TRPM8 channels in the colon of rats with 6-OHDA-induced Parkinson’s disease
Parkinson’s disease (PD) is neurodegenerative disease, which is accompanied by degeneration of dopaminergic neurons in subtantia nigra. Non-motor symptoms, in particular, disorders of the gastrointestinal (GI) tract are observed in 20-80% of patients some 15-20 years before clinically diagnosed PD and are not a least important feature of PD pathogenesis. The transient receptor potential (TRP) channels are expressed throughout the GI tract, where they play an important role in taste, thermoregulation, pain, mucosal function and homeostasis, control of interstitial motility etc. The aim of this study was to investigate the contribution of TRPV4 and TRPM8 channels in the GI motor function in the colon of rats with PD, incduced by injection of the 12 μg 6-hydroxydopamine (6-OHDA). The studies were performed on the 4th week and the 7th month after PD induction The rats were randomly divided into: I group – the sham-lesioned rats, 4 μl 0.9% NaCl, autopsy 4 weeks after injection (n = 5); II group – the 6-OHDA-PD rats, 4 μl 12 μg of 6-OHDA, autopsy 4 weeks after injection (n = 5); III group – the sham-lesioned rats, 4 μl 0.9% NaCl, autopsy 7 months after injection (n = 4); IV group – the 6-OHDA-PD rats, 4 μl 12 μg of 6-OHDA, autopsy 7 months after injection (n = 5). We evaluated the body weight of rats, GI transit time, the cecum weight index and immunohistochemical identification of tyrosine hydroxylase (TH) -positive cells, and TRPV4, TRPM8 expression in rat’s colon. We showed that on the 7th month of the experiment, the GI transit time doubles over time; the cecum weight index of 6-OHDA rats increased by 57%; the number of TH-positive cells in colon rats decreased 2-fold, while TRPM8 ion channels were downregulated in PD rats and TRPV4 ion channels were upregulated in the colon of rats with 6-OHDA-PD. It was concluded that TRPV4 and TRPM8 ion channels may be considered pharmacological targets in the progression of PD pathology.
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