OLETF 쥐에서 Thiazolidinediones 투여가 발기와 관련된 큰골반신경절 신경세포의 신경화학적 조성에 미치는 영향 = Effect of Thiazolidinediones Administration on Neurochemical Composition of MPG Neurons Related to Erection in OLETF Rat

국문 초록 (Abstract)

음경해면체 혈관의 내피세포와 nonadrenergic noncholinergic 신경종말에서 분비되는 nitric oxide는 발기를 매개하는 주된 전달물질이며, 신경전달물인 acetylcholine와 vasoacitive interestinal phlypeptide (VIP)도 발기를 매개하는데 중요한 역할을 한다고 보고되어 있따. 자율신경병증은 발기부전을 일으키고 체감각운동 신경병증과 자율신경병증을 포함하는 다발신경병증을 나타내는 당뇨환자들에게 이러한 발기부전이 일어난다. Thiazolidinedione (TZD)는 제2형 당뇨병에서 인슐린 저항성을 개선시키는 약물이며, 당뇨병콩팥병증을 개선하고 혈당을 낮추며 혈압을 감소시킨다고 알려져 있다. 그러나 발기부전과 관련된 신경병증에 대한 이 약물의 효과는 아직까지 알려진바 없다. 이 연구는 발기부전과 관계가 있는 신경병증에서 TZDs 계열 약물인 pioglitazone 또는 rosiglitazone 약물투여 후 큰골반신경절에서 신경전달물질 구성의 변화를 실험하였고 대조군으로 유전적으로 당뇨가 유발되지 않는 Long Evans Tokushima Otsuka (LETO) 쥐를 사용하였다. 형태계측에 의해 LETO 군, OLETF 군 그리고 pioglitazone 투여 OLETF 군 또는 rosiglitazone 투여 OLETF 군의 큰골반신결절에서 Nitric oxide synthase (NOS), throsine hydroxylase (TH), VIP 그리고 neuropeptide Y (NPY) 등의 신경전달물질들이 변화를 측정하였다. NOS, TH 그리고 VIP 면역반응 신경세포의 수는 LETO 군의 비교하여 OLETF 군의 큰골반신경절에서 감소하였고, 반면에 음경혈관들의 혈관수축을 조절하는 NPY 면역반응 신경세포의 수는 LETO 군과 비교화여 OLETF 군의 큰골반신경절에서 증가하는 것으로 나타났다. 23주간 pioglitazone 또는 rosiglitazone을 투여한 OLETF 군에서의 개체간의 약간의 차이는 있었지만 LETO 군과 같은 수준으로 회복하였다. 이 결과들은 TZDs 투여가 발기부전과 관련된 자율신경병증의 치료를 위해 도움을 줄 것이라고 여겨진다.

다국어 초록 (Multilingual Abstract)

The main transmitter substance mediating erection is the nitric oxide released from the vascular end-othelial cells of corpus cavernosum and from the nonadrenergic, noncholinergic nerve endings. In addition, some neuro-transmitters, such as acerylcholine or vasoactive intestinal polypeptide(VIP), have been reported to play an important role in mediating the erection. Thus, autonomic neuropathy may cause erectile dysfunctionm and in reality, it occurs frequently in individuals with diabetes mellitus(DM), in which polyneuropathy, including both peripheral somatic sensorimotor neuropathy and autonomic neuropathy, develops usually. Thiazolidinedione(TZD) is an insulin-sensitizing agent used for the treatment of type 2 DM with insulin resistance, and has been reported ameliorate nephropathy, decrease plasma glucose level and reduce blood pressure. However, the effect of this drug on the neuropathy related to erectile dysfunction has never been proved. In the present study, to evaluate the effect of TZDs on the neuropathy concerned with erectile dysfunction, we examined neurochemical changes of major pelvic ganglion (MPG) neurons in Otsuka Long Evans Tokushima Fatty (OLETF) rats, genetic models with non-insulin-dependent DM, after(TZD)s(pioglitazone and rosiglitazone) treatment. Age-matched nondiabetic Long Evans Tokushima Otsuka(LETO) rats were used as controls. Nitric Oxide synthase(NOS), tyrosine hydroxylase(TH), VIP, and neuropeptide Y (NPY) contents were measured in MPG neurons of LETO, OLETF and pioglitazone- or rosiglitazone-treated OLETF rats by morphometry. Compared to the correspondign LETO group, number of TH-, NOS- and VIP-immunoreactive(ir) neurons decreased, while that of NPY-ir neurons, which modulate noradrenergic vasoconstriction of penile arteries, increased in the MPG of the OLETF group. After administration of pioglitazone- or rosiglitazone to OLETF rats for 23 weeks, these neuronchemical changes were recovered to the control levels of the LETO group, although some variations were accompanied. These results suggest that TZDs treatment may be helpful for the treatment of autonomic neuropathy concerned with erectile dysfunction.

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