[논문]MPTP 유발 파킨슨 병 동물 모델에서의 신수혈(<tex>$BL_{23}$</tex>) 봉독약침의 항염증 효과

김찬영; 이재동; 이상훈; 고형균

MPTP 유발 파킨슨 병 동물 모델에서의 신수혈($BL_{23}$) 봉독약침의 항염증 효과
Anti-inflammatory Effect of Bee Venom Acupuncture at Sinsu($BL_{23}$) in a MPTP Mouse Model of Parkinson Disease 원문보기

大韓鍼灸學會誌= The journal of Korean Acupuncture & Moxibustion Society, v.26 no.4, 2009년, pp.49 - 58

김찬영 (경희대학교 한의과대학 침구학교실) , 이재동 (경희대학교 한의과대학 침구학교실) , 이상훈 (경희대학교 한의과대학 침구학교실) , 고형균 (경희대학교 한의과대학 침구학교실)

초록
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목적 : 파킨슨 병은 기저핵 흑질의 치밀부에서 도파민성 신경세포의 퇴행으로 인하여 발생하는 질병으로 신경 염증이 주요 병인으로 밝혀져 있다. 이 연구는 MPTP 유발 파킨슨 병 동물 모델에서 신수혈($BL_{23}$)에 대한 봉독 약침의 항염증 효과 및 그 기전을 확인하기 위해 시행되었다. 방법 : $C57_{BL}$/6쥐를 무처치군, MPTP+saline군, MPTP+BVA(0.06mg/kg)군, MPTP+BVA(0.6mg/kg)군의 4군으로 나눈 뒤 무처치군을 제외한 모든 그룹에 총 8시간 동안 2시간 간격으로 MPTP-HCl(20mg/kg per dose$\times$4)을 복강내로 주입하였다. MPTP+BVA 군에서 봉독약침은 마지막 MPTP 주입 2시간 후부터 48시간 간격으로 신수혈($BL_{23}$)에 양측으로 각 20${\mu}\ell$씩 주입하였고 MPTP+saline군에서는 봉독약침 대신 Saline을 주입하였다. 마지막 MPTP 주입 후 7일째에 쥐의 뇌를 적출한 후 면역조직화학법을 시행하였다. 결과 : MPTP 유발 파킨슨 병 동물 모델에서 신수혈에 대한 봉독약침은 농도 의존적으로 TH-Immunoreactivity neuron의 감소와 microglial activation을 억제하였다. HSP70-IR neuron은 모든 군에서 나타나지 않았다. 결론 : 봉독약침이 용량의존적으로 microglial activation을 억제하는 효과를 통해 도파민성 신경세포의 파괴를 억제함으로써 항염 효과를 나타냄을 알 수 있었다. 이 결과는 봉독약침이 microglial activation 억제를 통해 임상적으로 파킨슨 병과 같은 신경 퇴행성 질병에 있어 유용한 치료수단이 될 수 있음을 시사한다.

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가설 설정

In this study, we used an MPTP-induced neuroinflammation mouse model to examine whether if (a) BVA inhibits the loss of tyrosine hydroxylase (TH)-positive neurons as a result of its inhibition of microglial activation or induction of HSP70 synthesis and (b) the effect of BVA is dose dependent. Microglial activation was measured by the level of macrophage antigen complex(MAC-1) expression.

제안 방법

At the beginning of the experiment, the animals were randomly divided into four groups: A naïve group, an MPTP+saline group, an MPTP+ BVA(0.06mg/kg) group and an MPTP+BVA(0.6mg/kg) group.
At the beginning of the experiment, the animals were randomly divided into four groups: a naïve group, an MPTP+saline group, an MPTP+BVA(0.06mg/kg) group and an MPTP+BVA(0.6mg/kg) group.
16²⁷⁾, lateral to the roots of the third cranial nerve separating the medial and lateral SNpc. Evaluation of the neuronal staining intensity was performed by measuring the optical density of MAC-1-IR and HSP70-IR neurons in 10 sections from the substantia nigra. The optical density of the stained neurons was quantitatively assessed by microdensitometry using an image analyzer(Multiscan, Fullerton, CA, USA).
Immunohistochemical staining with TH antibody was performed on the brain samples collected from each group 7days after the last MPTP injection. TH-IR neurons were counted bilaterally at least three TH-immunostained mesencephalic sections.
To determine whether the beneficial effect of BVA was associated with HSPs, we examined the expression of HSP70, 7days after last MPTP injection.
To determine whether the beneficial effect of BVA was associated with inhibition of the MPTP-induced glial response, we examined the expression of MAC-1, a marker of microglial activation, 7days after last the MPTP injection.

대상 데이터

Six-week old male C57BL/6 mice(Samtaco Co., Korea), weighing 20－25g, were used in all experiments. The mice were acclimated for 2 weeks in cages at 21°C and were provided with water and food ad libitum.

데이터처리

To rule out a possible change in SNpc volume as an influencing factor, the number of TH-IR neurons are expressed as a ratio of normal controls per area of SNpc. Statistical analyses were performed using analysis of variance (ANOVA). A Bonferroni Multiple Comparison Test was used to compare individual means.

이론/모형

Statistical analyses were performed using analysis of variance (ANOVA). A Bonferroni Multiple Comparison Test was used to compare individual means. Differences between the means of experimental groups were considered significant at p<0.

성능/효과

In conclusion, we found that BVA at BL23 inhibited MPTP-induced neuronal loss of TH-IR neurons and microglial activation in the SNpc of a mouse PD model, and that this suppression occurred in a dose dependent manner.

후속연구

HSP70-IR cells were not observed in the SNpc of any of the tested groups. However, since the only observation was made 7days after the last MPTP injection, further research, including observation at different time points, is required.

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