실험적으로 유발시킨 면포에 대한 13-Cis-Retinoic Acid의 효과

Abstract

[한글]

13-cis-retinoic acid는 vitamin A의 합성 유도체로서 좌창, 특히 종래의 여러 치료방법에 의해 잘 치료되지 않았던 낭포성 또는 응피성 좌창의 치료에 그 우수한 효과가 있음이 증명되었다 (Peck등, 1979 ; Farrelle등, 1980 ; Plewig 및 Wagner, 1981 ; 1982). 이

약물의 작용 기전은 잘 알려져 있지 않으나 피지선 억제작용 (Peck등, 1978 ; Strauss등, 1980 ; Gomez 및 Moskowitz , 1980). 항염증작용(Pltewig 및 Wagner, 1981 ; Plewig등, 1982), g항균작용(Plewig등, 1982), 이상각화 (abnormalkeratinization)에 대한 작용 (Plewig등, 1981, 1982) 등이 알려져 있다.

이에 13-cis-retinoic acid의 이상 각화에 대한 작용을 관찰하고저, 실험적으로 면포 (comedo)를 유발시켜 이 약물의 효과를 Planimeter, 광학현미경 및 주사전자현미경을 사용하여 관찰하였다.

면포를 유발시키기 위하여 유성절삭유(insoluble cutting oil)을 매일 1회 2주간 도포하였으며, 면포형성 후 대조군 , 13-cis-retinoic acid 2㎎/㎏/day 투여군 및 20㎎/㎏/day 투여군으로 나누어 실험하였다. 대조군은 콩기름 2㎖만을, 그리고 13-cis-retinoic aci

d 투여군은 13-cis-retinoic acid를 각각 2㎎/㎏, 20㎎/㎏Tlr 콩기름에 녹여 매일 1회 4주간 경구투여하였다.

13-cis-retinoic acid의 면포에 대한 효과는 면포의 넓이변화를 planimeter로 측정하고, 면포의 형태변화를 광학현미경과 주사전자현미경으로 관찰하였으며, 그 결과는 다음과 같다.

1. 유성절삭유 도포 2주후 모든 실험동물에서 면포가 형성됨을 육안적으로 관찰할 구 있었으며, 광학현미경적 소견상 표피 및 진피의 비후, 모낭상피의 증식, 피지선의 현저한 위축을 관찰할 수 있었으며, 모낭관은 현저히 팽대되었고, 관상 또는 소용돌이 형태로

밀집되어있는 각질세포로 차있음을 볼 수 있었다. 면포의 넓이는 유성절삭유 도포전에 비하여 10배 가량 증가되었다. 그리고 주사전자현미경적 소견상 면포는 각질세포들이 모여 마치 국화꽃과 같은 형태를 이루고 있었다.

2. 광학현미경적 소견상 면포형성 4주후 대조군에 비하여 13-cis-retinoic acid 20㎎/㎏/day 투여군에서 팽대되었던 모낭관의 길이 및 폭이 현저히 감소되었으며, 그 안은 비교적 느슨한 소량의 각질세포로 차있었으나, 피지선크기의 증가는 동일하였음을 관찰할 수 있었고, 2㎎/㎏/day 여군에서는 뚜렷한 조직학 차이가 없었다.

3. 면포의 넓이는 면포형성 4주후 대조군과 13-cis-retinoic acid 2㎎/㎏/day 투여군 간에는 의의있는 차이가 없었으나, 이 두군과 13-cis-retinoic acid 2㎎/㎏/day 투여군 사이에서는 통계학적으로 의의있는 차이가 있었다.

4. 주사전자현미경적 소견상 면포형성 4주후 대조군에서 면포는 각질세포들이 비교적 단단히 결합하여 부분적으로 국화꽃모양을 이루고 있었으나, 13-cis-retinoic acid 2㎎/㎏/day 투여군에서는 국화꽃모양의 면포를 거의 관찰할 수 없었고 대조군에 비해 면포의

직경에는 차이가 없었으나 그 높이는 현저히 감소됨을 볼 수 있었다. 13-cis-retinoic acid 2㎎/㎏/day 투여군에서는 면포가 국화꽃모양을 완전히 소실하였으며, 대조군에 비해 직경 및 높이가 현저히 감소되어, 모낭주위의 각질세포들이 탈락되어 거친 표피표면을 이

루고 있는 소견을 제외하고는 유성절삭유 도포전 소견과 거의 유사함을 관찰할 수 있었다. 이상과 같은 소견으로 보아, 유성절삭유에 의해 유발된 면포에 대하여 13-cis-retinoic

acid의 이상각화에 대한 작용이 있음을 관찰할 수 있었으며, 이는 아마도 VAA 국소도포에서와 같이 각질세포사이의 결합력을 감소시킴으로서 나타나지 않나 추측되며, 그 작용효과는 약물투여량과 관계가 있음을 관찰할 수 있다.

The Effect of 13-Cis-Retinoic Acid on Experimentally Induced Comedones of Rabbits

Byoung Moon Choi

Department of Medical Science The Graduate School Yonsei University

(Directed by Professor Sungnack Lee, M.d)

The effect of 13-cis-retinoic acid, which is clinically Very effective in the

treatment of severe acne, on experimentally induced comedones was studied by means

of histology, planimetry, and scanning electron microscope.

To induce comedo formation, the insoluble cutting oil was applied for 2 weeks to

the ears of adult male albino rabbits just external to the ear canal. After comedo

formation, 13-cis-retinoic acid was fed by feeding tube to rabbits daily for 4

weeks. A low dose of 2㎎/㎏ and a high dose of 20㎎/㎏ body weight were selected.

Soy-bean oil served as the vehicle.

The results are summarized as follows:

1. The topical application of insoluble cutting oil caused a marked follicular

accentuation in all the experimental animals at 2 weeks. Microscopically,

thickening of the epidermis, proliferation of the epithelium of the follicles and

sebaceous gland ducts, diminution of the sebaceous gland acini, and dermal

thickening were evident. The follicular lumen was greatly distended by very compact

and adherent horny cells. The scanning electron microscope clearly showed the

comedo projecting as a chrysanthemum flower-like structure.

2. Planimetrically, the high dose of 13-cis-retinoic acid led to a significant

decrease in size of comedones in comparison to the soy-bean oil control group and

the group treated with the low dose of 13-cis-retinoic acid for 4 weeks (P <

0.001).

3. In the group treated with high dose of 13-cis-retinoic acid. the size of

follicle was drastically reduced and the lumen contained a small amount of loose,

non-adherent horny cells ; while the group treated with low dose of 13-cis-retinoic

acid showed similar histological changes as the soy-bean oil control.

4. In scanning electron microscopic study of the group treated with high dose of

13-cis-retinoic acid, the comedo was no longer a compact chrysanthemum flower like

structure and its component cells were only loosely adherent. In the group treated

with low dose of 13-cis-retinoic acid, the height of comedones was markedly

decreased, but the diameter wasn't decreased in comparison to the soy-bean oil

control .

From these findings, it is clear that the action of oral 13-cis-retinoic acrid on

experimental comedones induced by insoluble cutting oil is the reduction of

abnormal keratinization, probably resulting from the decreased cohesiveness between

horny cells as seen in the topical vitamin A acrid application. The therapeutic

effect of 13-cis-retinoic acid is dose-dependent.

[영문]

The effect of 13-cis-retinoic acid, which is clinically Very effective in the treatment of severe acne, on experimentally induced comedones was studied by means of histology, planimetry, and scanning electron microscope.

To induce comedo formation, the insoluble cutting oil was applied for 2 weeks to the ears of adult male albino rabbits just external to the ear canal. After comedo formation, 13-cis-retinoic acid was fed by feeding tube to rabbits daily for 4

weeks. A low dose of 2㎎/㎏ and a high dose of 20㎎/㎏ body weight were selected.

Soy-bean oil served as the vehicle.

The results are summarized as follows:

1. The topical application of insoluble cutting oil caused a marked follicular accentuation in all the experimental animals at 2 weeks. Microscopically, thickening of the epidermis, proliferation of the epithelium of the follicles and

sebaceous gland ducts, diminution of the sebaceous gland acini, and dermal thickening were evident. The follicular lumen was greatly distended by very compact and adherent horny cells. The scanning electron microscope clearly showed the comedo projecting as a chrysanthemum flower-like structure.

2. Planimetrically, the high dose of 13-cis-retinoic acid led to a significant decrease in size of comedones in comparison to the soy-bean oil control group and the group treated with the low dose of 13-cis-retinoic acid for 4 weeks (P < 0.001).

3. In the group treated with high dose of 13-cis-retinoic acid. the size of follicle was drastically reduced and the lumen contained a small amount of loose, non-adherent horny cells ; while the group treated with low dose of 13-cis-retinoic

acid showed similar histological changes as the soy-bean oil control.

4. In scanning electron microscopic study of the group treated with high dose of 13-cis-retinoic acid, the comedo was no longer a compact chrysanthemum flower like structure and its component cells were only loosely adherent. In the group treated with low dose of 13-cis-retinoic acid, the height of comedones was markedly decreased, but the diameter wasn't decreased in comparison to the soy-bean oil control .

From these findings, it is clear that the action of oral 13-cis-retinoic acrid on experimental comedones induced by insoluble cutting oil is the reduction of abnormal keratinization, probably resulting from the decreased cohesiveness between horny cells as seen in the topical vitamin A acrid application. The therapeutic

effect of 13-cis-retinoic acid is dose-dependent.