실험적 당뇨병 쥐에서 음경 해면체와 신경의 형태학적 변화

Abstract

[한글]

당뇨병 환자의 약 50%가 발기부전을 호소하며 발기부전의 원인으로 신경성 및 혈관성 원인이 단독 또는 복합적으로 결부되어 나타나며 당뇨병에 특징적인 신경병증 및 혈관병증의 소견에 대한 기술이 보고자에 따라 차이가 있다.

본 연구는 streptozotocin(STZ)으로 유발한 당뇨병 흰쥐의 음경 해면체와 신경의 형태학적변화를 관찰함으로써 당뇨병으로 인한 발기부전의 병인을 규명하여 당뇨병성 발기부전 치료에 도움이 되고자 하였으며, 본 실험적 당뇨병 흰쥐가 당뇨병성 발기부전의 실험

모형이 될 수 있는지 알아보고자 하였다.

실험적 당뇨병은 Sprague-Dawley 흰쥐에 STZ(65mg/kg)을 복강내 주사하여 유발하였고 발기능을 평가하기 위한 간접적 방법으로 교미실험을 시행하였다. 당뇨병 유발 4주, 8주, 12주에 실험동물의 음경을 적출하여 일반염색, 특수염색 및 면역조직화학염색을 실시하

고 해면 신경의 신경주위막내 수초와 핵의 수적 변화를 형태계측기로 관찰하고 해면 신경과 배부 동맥을 전자현미경으로 관찰하여 다음과 같은 결과를 얻었다.

1. STZ 유발 당뇨병 흰쥐는 대조군에 비해 체중이 통계적으로 의의있게 감소되었다.

2. 당뇨병 흰쥐는 대조군에 비해 교미활동이 전반적으로 감소되었으며, 당뇨병 유발 12주에는 통계적으로 의의있는 교미활동의 감소를 보였다.

3. 당뇨병 흰쥐 해면 신경의 신경주위막내 핵 및 수초 수의 감소를 보였다. 배부 동맥은 내탄성막과 혈관벽이 얇아졌으며 해면체내 동양혈관은 확장되었고 동양혈관 주위의 평활근과 교원질은 감소되었다.

4. Vasoactive intestinal polypeptide(VIP), norepinephrine. acetylcholinesterase 양성 신경은 주로 신경 다발에서 관찰되었고, 백막에서는 거의 관찰되지 않았다. 혈관에서는 외막과 중막의 경계에서 관찰되었다. 농도계측 결과 콜린성 및 VIP성 해면 신경의

염색농도는 대조군에 비해 당뇨병 유발 8주부터 감소되었으나 아드레날린성 해면 신경의 염색농도는 차이가 없었다.

5. 전자현미경 소견상 당뇨병 흰쥐 해면 신경의 변성은 당뇨병 유발 4주부터 시작되었다. Schwann 세포, 신경주위 세포와 배부 동맥의 기저막은 당뇨병 유발 8주부터 비후되었다.

본 실험의 결과로 보아 STZ 유발 당뇨병 흰쥐는 신경 및 혈관에 변성이 일어나고, 콜린성 신경 및 VIP성 신경의 감소와 아드레날린성 신경의 상대적 증가로 발기부전이 초래되는 것으로 생각되며, STZ 유발 당뇨병 흰쥐는 당뇨병성 발기부전의 실험적 모형이 될 수

있다고 생각한다.

Morphological changes in corpora cavernosa and nerves of experimental diabetic rats

Jin Seon Cho

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professor Hyung Ki Choi)

The incidence of impotence in diabetic patients has been reported to be about 50

per cent. Erectile dysfunction in patients with diabetes is related to penile

autonomic neuropathy and/or microangiopathy.

In this study morphological changes of nerves and vessels of corpora cavernosa in

streptozotocin-induced diabetic rats were examined to study pathogenesis of diabtic

impotence and further, to prove the usefulness of this model for the study of

diabetic impotence.

The diabetic impotence was evaluated by mating test. The changes of dorsal

arteries, cavernosa and cavernous nerves containing catecholamine, vasoactive

intestinal polypeptide(VIP) and acetylcholin-esterase were examined at 4-, 8-, and

12-week after induction of diabetes using histological, immunohistochemical and

morphometric techniques.

The following results were obtained;

1. The weights of diabetic rats remained significantly lower than that of control

rats throughout the experimental period.

2. At the 12th week of diabetes, the mating rate of diabetic rats was

significantly reduced.

3. Dorsal arteries of diabetic rats showed reduced internal elastic membrane and

thinned arterial wall. Whithin the corpora cavernosa of diabetic rats, the mass of

smooth muscle was reduced, intercommunicating vascular spaces were enlarged and

waved collagen bundles were thin and sparse. A significant reduction in the number

of myelin sheaths and nuclei was observed in the cavernous nerves of diabetic rats

from 4 weeks after diabetes induction.

4. A significant reduction in the density of acetylcholinesterase ans

VIP-immunoreactive nerves was observed in the cavernous nerves of diabetic rats

from 8 weeks after diabetes induction. However, no change was observed in the

density of norepinephrine-immunoreactive nerves.

5. There was marked thickening of the basement membrane of dorsal arteries,

Schwann cells and perineurial cells of diabetic rats from 8 weeks after diabetes

induction.

From the above results, disbetes resulted in diabetic microangiopathy and

neuropathy in which cholinergic and VIPergic nerves but not adrenergic nerves were

reduced in diabetic rats, which may be regared as important causes of diabetic

impotence. It is suggested that streptozotocin-induced diabetic rats are suitable

for the study of diabetic impoence.

[영문]

The incidence of impotence in diabetic patients has been reported to be about 50 per cent. Erectile dysfunction in patients with diabetes is related to penile autonomic neuropathy and/or microangiopathy.

In this study morphological changes of nerves and vessels of corpora cavernosa in streptozotocin-induced diabetic rats were examined to study pathogenesis of diabtic impotence and further, to prove the usefulness of this model for the study of diabetic impotence.

The diabetic impotence was evaluated by mating test. The changes of dorsal arteries, cavernosa and cavernous nerves containing catecholamine, vasoactive intestinal polypeptide(VIP) and acetylcholin-esterase were examined at 4-, 8-, and

12-week after induction of diabetes using histological, immunohistochemical and morphometric techniques.

The following results were obtained;

1. The weights of diabetic rats remained significantly lower than that of control rats throughout the experimental period.

2. At the 12th week of diabetes, the mating rate of diabetic rats was significantly reduced.

3. Dorsal arteries of diabetic rats showed reduced internal elastic membrane and thinned arterial wall. Whithin the corpora cavernosa of diabetic rats, the mass of smooth muscle was reduced, intercommunicating vascular spaces were enlarged and

waved collagen bundles were thin and sparse. A significant reduction in the number of myelin sheaths and nuclei was observed in the cavernous nerves of diabetic rats from 4 weeks after diabetes induction.

4. A significant reduction in the density of acetylcholinesterase ans VIP-immunoreactive nerves was observed in the cavernous nerves of diabetic rats from 8 weeks after diabetes induction. However, no change was observed in the

density of norepinephrine-immunoreactive nerves.

5. There was marked thickening of the basement membrane of dorsal arteries, Schwann cells and perineurial cells of diabetic rats from 8 weeks after diabetes induction.

From the above results, disbetes resulted in diabetic microangiopathy and neuropathy in which cholinergic and VIPergic nerves but not adrenergic nerves were reduced in diabetic rats, which may be regared as important causes of diabetic

impotence. It is suggested that streptozotocin-induced diabetic rats are suitable for the study of diabetic impoence.