[논문]돈태반 효소 가수분해물의 cyclophosphamide에 의한 면역 저하 동물 모델에 미치는 면역 증진 효과

김건남; 김민주; 윤선명; 권민주; 신동엽; 이학용; 박영미

doi:10.9721/kjfst.2022.54.2.155

돈태반 효소 가수분해물의 cyclophosphamide에 의한 면역 저하 동물 모델에 미치는 면역 증진 효과
Immunostimulatory effects of enzymatic porcine placental hydrolyzate against cyclophosphamide-induced immunosuppressed model 원문보기

한국식품과학회지 = Korean journal of food science and technology, v.54 no.2, 2022년, pp.155 - 162

김건남 (유니메드제약) , 김민주 (유니메드제약) , 윤선명 (유니메드제약) , 권민주 ((주)인비보) , 신동엽 ((주)인비보) , 이학용 ((주)인비보) , 박영미 ((주)인비보)

초록
AI-Helper

본 연구는 돈태반 효소 가수분해물의 면역증진 효과를 확인하고자 Cy를 이용한 면역 저하 모델에서 농도별 돈태반 효소 가수분해물을 투여한 실험군의 주간 체중과 조직 중량, 혈중 면역세포(백혈구, 과립구, 림프구, 중간구) 함량, 혈중 cytokine 및 immunoglobulin 함량, 자연살해세포 활성, 비장 조직 분석을 수행하였다. 체중은 대조군과 비교하여 돈태반 효소 가수분해물을 투여한 실험군 중 중농도 투여군(1.03 mg/kg BW, total nitrogen)과 고농도 투여군(2.07 mg/kg BW, total nitrogen)에서 다소 증가하는 경향을 보였고, 조직 중량은 돈태반 효소 가수분해물을 투여한 실험군이 Cy만을 단독 투여한 대조군에 비해 다소 높았으며, 이 중 고농도 투여군은 비장과 흉선 조직 중량 모두에서 대조군보다 유의적으로 높게 조사되었다. 각 실험군별 비장 조직을 이용한 자연살해세포 활성 분석 결과 정상군에 비해 대조군은 유의하게 감소하였으나 돈태반 효소 가수분해물을 고농도로 투여한 실험군과 양성대조군은 대조군에 비해 증가하는 경향을 보여 정상군과 유사한 수준을 보였다. 일반 혈액학적 분석(CBC analysis)에서 돈태반 효소 가수분해물을 투여한 실험군은 대조군에 비해 백혈구와 과립구, 림프구 및 중간구에서 모두 높은 함량을 보이는 것으로 나타났는데, 특히 고농도 투여군은 백혈구의 경우 양성 대조군인 HemoHIM 투여군과 유사한 수준으로, 과립구와 중간구의 경우 양성대조군보다 더 높은 함량을 보이는 것으로 조사되었다. 혈중 cytokine과 immunoglobulin의 함량을 분석한 결과 돈태반효소 가수분해물을 투여한 실험군에서 혈중 TNF-α와 IL-1β, IL-2, IL-12 및 IgG의 함량을 대조군과 비교하여 유의하게 증가시키거나 증가시키는 경향을 보였다. 또한 조직학적 분석에서 비장조직은 대조군에서 관찰되던 백색수질의 붕괴와 적색수질에서의 세포 응축현상은 돈태반 효소 가수분해물을 투여한 실험군에서 점차 호전되는 경향을 보였다. 이러한 결과를 바탕으로 돈태반효소 가수분해물은 Cy로 인한 세포와 조직 손상을 감소시키고 혈중 면역 관련 인자들의 함량을 증가시켜 면역력을 증진시키는데 긍정적인 영향을 미치는 것으로 판단되며, 추후 이를 활용한 건강 기능성 개발 및 의약품 개발에 따른 활용가치가 매우 높을 것으로 생각된다.

Abstract ▼ AI-Helper

This study investigated the immunostimulatory effect of enzymatic porcine placental hydrolyzate (EPPH) in cyclophosphamide (Cy)-treated rats. This effect of EPPH prevented Cy-induced decreases in body, spleen, and thymus weights and natural killer (NK) cell activity. The numbers of immune cells, such as white blood cells, granulocytes, and lymphocytes, and mid-range absolute counts were significantly higher compared to the control group. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-2, IL-12, and immunoglobulin G (IgG) were notably reduced by Cy, while EPPH prevented these effects. Histopathological analysis of spleen samples revealed the protective effect of EPPH against Cy-induced immunosuppression. The findings demonstrate that EPPH can alleviate immunosuppression by cell viability, tissue damage, and regulation of the levels of cytokines. EPPH may have value as a component of immunostimulatory agents or an ingredient in functional foods.

주제어

표/그림 (6)

그림 Fig. 2. Effect of EPPH on the spleen and thymus weight of cyclophosphamide-induced immunosuppressed rats. Spleen weight with (A) absolute weight and (B) relative weight, thymus weight with (C) absolute weight and (D) relative weight. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks, after which spleen and thymus were collected for analysis. Bars labeled with different superscripts have significantly different values (p<0.05).
그림 Fig. 1. Effect of EPPH on the body weight of cyclophosphamideinduced immunosuppressed rats. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks. Bars labeled with different superscripts have significantly different values (p<0.05).
그림 Fig. 3. Effect of EPPH on NK cell activity in cyclophosphamideinduced immunosuppressed rat splenocytes. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks, after which spleen were collected for analysis. Splenocytes were cocultured with target cells (AR42J) in 96-well plates. Next, the cell were incubated for 24 h in a 5% CO₂ incubator with a ratio of effector to target cells of 20:1. The NK cell activity was calculated as the survival rate of AR42J compared to that of the control group. Bars labeled with different superscripts have significantly different values (p<0.05).
그림 Fig. 4. Effects of EPPH on (A) white blood cell, (B) granulocyte, (C) lymphocyte and (D) mid size cells absolute counts in the whole blood of cyclophosphamide-induced immunosuppressed rats. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks, after which whole blood samples were collected for analysis. The levels of white blood cell, granulocyte, lymphocyte and mid size cells in the blood samples were determined using a Hemavet 950 system. Bars labeled with different superscripts have significantly different values (p<0.05).
그림 Fig. 5. Effect of EPPH on the serum levels of immune-related cytokines in the serum of cyclophosphamide-induced immunosuppressed rats. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks, after which serum levels of (A) TNF-α, (B) IL-2, (C) IL-12, (D) IL-1β and (E) IgG were quantified using ELISA kits. Bars labeled with different superscripts have significantly different values (p<0.05).
그림 Fig. 6. Effect of EPPH on immunity-associated spleen damage in cyclophosphamide-induced immunosuppressed rats. Wistar rats were treated with saline, cyclophosphamide (Cy; 5 mg/kg/day), and oral EPPH (0, 2.06, 1.03, or 2.07 mg total nitrogen/kg/day) once daily for 4 weeks, after which spleen damage was analyzed histologically. Representative images of the sectioned spleens of (A) normal rats (saline treatment), (B) control rats (treated with only Cy), and (C-E) EPPH-treated rats [treated with Cy and (C) 0.26 mg/kg, (D) 1.03 mg/kg, or (E) 2.07 mg/kg EPPH]. Scale bar=100 μm. CV, central vein; LN, lymph nodule; MZ, marginal zone; RP, red pulp.

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