口服草药来源的小RNA(XKC-sRNA-h3)可治疗血管紧张素Ⅱ诱导的小鼠高血压

Oral administration of the herbal oligonucleotide XKC-sRNA-h3 prevents angiotensin II-induced hypertension in mice

高血压是心血管疾病发病和死亡的重要危险因素之一,也是全球公共卫生关注的焦点.目前,寡核苷酸药物已被证明可用于多种疾病治疗,是未来极有前景的药物研发方向.本研究展示了一条草药来源的小RNA(small RNA, sRNA)——XKC-sRNA-h3(B55710460, F221.I000082.B11),通过靶向血管紧张素转换酶(angiotensin-converting enzyme, ACE)基因而在高血压小鼠模型中有显著的降压效果.相比降压药卡托普利,口服鞘氨醇(d18:1)-XKCsRNA-h3本草体可以更有效地缓解血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)诱导的小鼠高血压性心脏损伤和肾脏损伤.这些结果表明, XKC-sRNA-h3有望成为一种新型可口服治疗高血压的ACEI类寡核苷酸药物.

Hypertension has become a growing public health concern worldwide.In fact,hypertension is commonly associated with increased morbidity and mortality.Currently,oligonucleotide drugs have proven to be promising therapeutic agents for various diseases.In the present study,we aimed to demonstrate that a herbal small RNA(sRNA),XKC-sRNA-h3(B55710460,F221.1000082.B11),exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme(ACE)in mice.When compared with captopril,oral administration of the sphingosine(d18:1)-XKC-sRNA-h3 bencaosome more effectively prevented angiotensin Ⅱ-induced hypertensive cardiac damage and alleviated kidney injury in mice.Such findings indicated that XKCsRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.