首页|桑椹来源的寡核苷酸显著改善小鼠骨质疏松症

桑椹来源的寡核苷酸显著改善小鼠骨质疏松症

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本试验旨在探究桑椹来源的寡核苷酸ASON-OP对小鼠骨质疏松症的改善作用.将30只雌性小鼠随机分为5组,分别为假手术组、模型对照组、阳性药物组、ASON-OP组和ASON-NC组(ASON-NC为无义序列,作为阴性对照),每组6只.除假手术组小鼠以外,其他4组小鼠均进行双侧卵巢切除(OVX),构建骨质疏松症小鼠模型.建模成功后,继续饲养1周,而后进行给药处理.假手术组和模型对照组每天灌胃300 μL生理盐水;阳性对照组皮下注射特立帕肽,剂量为80 μg/(kg BW·d),l周给药5次;ASON-NC组每天灌胃ASON-NC溶液,剂量为 2 mg/(kg BW·d);ASON-OP 组每天灌胃 ASON-OP 溶液,剂量为 2 mg/(kg BW·d).连续给药4周后,检测小鼠骨组织微结构、骨转化指标等.结果显示:与模型对照组和ASON-NC组相比,连续4周灌胃寡核苷酸ASON-OP显著增加了 OVX小鼠的骨密度(P<0.05);显著提高了OVX小鼠血清成骨因子骨钙素(OCN)含量(P<0.05),显著降低了血清破骨因子Ⅰ型胶原C末端肽(CTX-1)含量(P<0.05);显著提高了 OVX小鼠股骨中促进成骨相关基因Runt相关转录因子2(Runx2)、肝/骨/肾型碱性磷酸酶(Alpl)、骨钙素(Bglap)的mRNA相对表达量(P<0.05).综上所述,桑椹来源的寡核苷酸ASON-OP具有显著的抗骨质疏松症作用.
Mulberry-Derived Oligonucleotides Significantly Improved Osteoporosis in Mice
The objective of this experiment was to explore the improvement effects of ASON-OP,an oligonu-cleotide derived from the mulberry.Thirty female mice were randomly divided into five groups:sham surgery group,model control group,positive control group,ASON-OP group,and ASON-NC group(ASON-NC is a nonsense sequence,as negative control),with six mice in each group.Except for the mice in the sham surgery group,bilateral ovariectomy(OVX)was performed on mice in the other four groups to induce the osteoporo-sis mouse model.After successful modeling,continued to feed for 1 week,and then administered the drug.Mice in the sham surgery group and model control group were given 300 μL normal saline per day by gavage;mice in the positive control group were injected subcutaneously with teriparatide at the dose of 80 μg/(kg BW·d),five times a week;mice in the ASON-NC group were given ASON-NC solution by ga-vage,2 mg/(kg BW·d);mice in the ASON-OP group were given ASON-OP solution by gavage,2 mg/(kg BW·d).The mice were continuously administered for 4 weeks,and their bone tissue microstruc-ture and bone turnover markers were measured.The results showed as follows:compared to the model control group and ASON-NC group,mice gavaged with oligonucleotide ASON-OP for 4 weeks significantly increased the bone mineral density of OVX mice(P<0.05);it significantly increased the serum content of osteocalcin(OCN)as a bone formation marker of OVX mice(P<0.05),and significantly decreased the serum content of type Ⅰ collagen C-terminal telopeptide(CTX-1)as a bone resorption marker(P<0.05);it also significantly increased the mRNA relative expression levels of the bone formation-related genes Runt-related transcription factor 2(Runx2),alkaline phosphatase,liver/bone/kidney(Alpl)and bone gamma-carboxyglutamate protein(Bglap)in the femur of OVX mice(P<0.05).In conclusion,ASON-OP,an oligonucleotide derived from mulberry,exhibits significant anti-osteoporotic effect.[Chinese Journal of Animal Nutrition,2024,36(1):602-609]

mulberryoligonucleotideASON-OPmiceosteoporosis

穆雪萌、杜芯仪、王彦超、金云峰、张嘉

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中国医学科学院北京协和医院骨科,北京 100010

中国医学科学院北京协和医学院基础学院,北京 100010

上海弗艾柏生物科技有限公司,上海 200433

北京优准生物科技有限公司,北京 110000

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桑椹 寡核苷酸 ASON-OP 小鼠 骨质疏松症

2024

动物营养学报
中国畜牧兽医学会

动物营养学报

CSTPCD北大核心
影响因子:1.297
ISSN:1006-267X
年,卷(期):2024.36(1)
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