Sodium Cromoglycate가 실험적 IgA신병증에 미치는 영향

Abstract

[한글]

IgA신병증은 임상적으로 반복성 재발성 혈뇨를 주된 증상으로 하고 면역병리학적으로 신사구체 맥관막 기질내 현저한 IgA의 침착을 특징으로 하는 질병으로서, 전세계적으로 발생하는 흔한 사구체 질환의 하나이며 우리나라에서도 비교적 많은 빈도로 발생한다. 그

러나 IgA신병증의 상세한 원인이나 발병기전에 대하여는 아직 이론이 많으며 형태학적 연구도 미흡한 실정이다. 최근 경구면역을 이용한 실험적 IgA신병증이 보고되고 있고 특히 점막면역기전의 관련성에 관하여 많은 관심을 모으고 있다.

이에 저자는 20gm내외의 자성 ddy 생쥐에 소아마비 백신을 경구(생백신) 및 비경구(비활성화백신)투여하여 IgA신병증의 유발을 시도함과 아울러, 비만세포에 작용하여 국소적 점막 면역반응을 억제하는 것으로 알려진 sodium cromoglycate(SCG)투여가 IgA신병증 유발에 미치는 영향을 조사함으로써 IgA신병증의 기전을 검토하고저, 백신투여 제 70일째 편측신적출술로 신사구체내에 침착된 IgA의 양을 관찰하고, 제 71일부터 100일까지 SCC를 첨가투여하거나 투여중지한 다음 도살하여 혈뇨, 단백뇨 및 혈청 IgA치를 측정하고 이미 침착된 IgA양의 변화를 광학현미경적, 면역형광현미경적, 및 전자현미경적으로 검색을 시행하여 관찰한 뒤 다음과 같은 결과를 얻었다.

1. 소아마비 백신의 경구 및 비경구 투여는 ddY생쥐에서 단백뇨, 혈청 IgA치 증가, 신사구체 맥관막 기질의 화장 및 맥관막 세포증식, 맥관막내 IgA의 침착, 그리고 전자현미경적으로 커다란 전자고밀도 물질의 침착을 수반하는 IgA신병증을 유발하였으며 이러한 변화는 경구 투여군보다 비경구 투여군에서 현저하였다.

2. 소아마비 백신 투여와 동시에 SCG를 투여한 경우에는 신사구체 맥관막내 IgA의 침착과 혈청 IgA치 그리고 전자고밀도 물질 침착 등이 백신만 투여한 경우보다 적었다.

3. 소아마비 백신을 투여한 군에서 제 71일 이후의 SCC투여중지 및 첨가투여는 IgA 침착정도에 뚜렷한 변동을 초래하지 않았으나, 혈청 IgA치는 SCG첨가투여로 감소 되었다.

이상의 소견을 종합하면 소아마비 백신을 생쥐에 경구 및 비경구 투여하여 IgA신병증을 유발할 수 있었으며, 이러한 IgA신병증 유발은 SCG동시 투여로 억제되지만, 이미 유발된 IgA신병증은 SCG투여로 호전되지 않았다.

The effect of sodium cromoglycate on experimental IBA nephropathy

So Young Jin

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professor In Joon Choi, M.D.)

IgA nephropathy is characterized clinically ,by recurrent hematuria and

immunopatho-logically by predominant deposits of IgA in the glomerular mesangium.

It is now recognized as a common form of nephritis throughout the world, and

several reports also suggest its frequent occurence in Korea. The etiology and

pathogenesis is not yet clearly defined, though the role of mucosal origin for the

mesangial IgA has been discussed by several authors. Recently, a few articles have

issued IgA nephropathy that was induced by passive oral immunization and assumpted

this finding as the participation of mucosal immunity.

In this study this author tried to induce mesangial IgA nephropathy in the mice

by oral or parenteral administration of the poliomyelitis vaccine, and then

investigated if IgA deposition could be prevented by concurrent use of sodium

cromoglycate (SCG). Sodium cromoglycate is known to have pharmacologic actions that

inhibit the local mucosal immune reaction by stabilization of the mast cell

membrane and prevention of degranulation.

Healthy female ddY mice were selected and divided randomly into six groups. Live

or inactivated poliomyelitis vaccines were administered in order to induce mucosal

and systemic immunization, respectively, and SCG was given together with the

poliomyelitis vaccine to identify whether SCG prevents the induction of mesangial

IgA deposit. A unilateral nephrectomy was performed on the 70th day. Mice were

divided into eleven groups and the administration of SCG wart or was not continued

as previously until the 100th day. On the each 70th and 10Oth day, urinary protein,

urinary RBC'a and serum IgA levels were obtained, and the kidneys were examined by

light, immunofluorescent and electron microscopes.

The results were as follows:

1. Mucosal immunity wart induced by the administration of poliomyelitis vaccine.

The findings were proteinuria, increase of serum IgA levels, mesangial cell

proliferation, mesangial matrix widening, glomerular mesangial deposits of IgA, and

large eleotron dense deposits in the mesangium. These changes were more marked in

the parenterally administered group.

2. Concurrent administration of SCG and the poliomyelitis vaccine resulted in a

significant decrease in mesangial IgA deposits, serum IgA levels and electron dense

deposits.

3. The presence or absence of SCG after the 70th day did net significantly

influenced on the glomerular mesangial IgA deposition. But serum IgA levels were

still decreased by the addition of SCG even alter the 70th day.

In summary, mesangial IgA nephropathy simulating IgA nephropathy in humans was

induced in ddY mice using poliomyelitis vaccine. Its induction was largely

prevented by the concurrent administration of SCG. Mesangial IgA deposits already

present were not cleared by the late administration of SCG.

[영문]

IgA nephropathy is characterized clinically ,by recurrent hematuria and immunopatho-logically by predominant deposits of IgA in the glomerular mesangium.

It is now recognized as a common form of nephritis throughout the world, and several reports also suggest its frequent occurence in Korea. The etiology and pathogenesis is not yet clearly defined, though the role of mucosal origin for the mesangial IgA has been discussed by several authors. Recently, a few articles have

issued IgA nephropathy that was induced by passive oral immunization and assumpted this finding as the participation of mucosal immunity.

In this study this author tried to induce mesangial IgA nephropathy in the mice by oral or parenteral administration of the poliomyelitis vaccine, and then investigated if IgA deposition could be prevented by concurrent use of sodium

cromoglycate (SCG). Sodium cromoglycate is known to have pharmacologic actions that inhibit the local mucosal immune reaction by stabilization of the mast cell membrane and prevention of degranulation.

Healthy female ddY mice were selected and divided randomly into six groups. Live or inactivated poliomyelitis vaccines were administered in order to induce mucosal and systemic immunization, respectively, and SCG was given together with the

poliomyelitis vaccine to identify whether SCG prevents the induction of mesangial IgA deposit. A unilateral nephrectomy was performed on the 70th day. Mice were divided into eleven groups and the administration of SCG wart or was not continued

as previously until the 100th day. On the each 70th and 10Oth day, urinary protein, urinary RBC'a and serum IgA levels were obtained, and the kidneys were examined by light, immunofluorescent and electron microscopes.

The results were as follows:

1. Mucosal immunity wart induced by the administration of poliomyelitis vaccine.

The findings were proteinuria, increase of serum IgA levels, mesangial cell proliferation, mesangial matrix widening, glomerular mesangial deposits of IgA, and large eleotron dense deposits in the mesangium. These changes were more marked in

the parenterally administered group.

2. Concurrent administration of SCG and the poliomyelitis vaccine resulted in a significant decrease in mesangial IgA deposits, serum IgA levels and electron dense deposits.

3. The presence or absence of SCG after the 70th day did net significantly influenced on the glomerular mesangial IgA deposition. But serum IgA levels were still decreased by the addition of SCG even alter the 70th day.

In summary, mesangial IgA nephropathy simulating IgA nephropathy in humans was induced in ddY mice using poliomyelitis vaccine. Its induction was largely prevented by the concurrent administration of SCG. Mesangial IgA deposits already

present were not cleared by the late administration of SCG.