柚皮素基于Th1/Th2轴对妊娠高血压大鼠症状的改善

Naringin ameliorates symptoms in pregnant hypertensive rats via Th1/Th2 axis

目的 分析柚皮素对改善妊娠高血压(PIH)大鼠症状和对子代生长的影响,并探讨可能的作用机制。方法 雌性大鼠随机分为模型组、柚皮素低剂量(50 mg·kg^(-1))、高剂量组(100 mg·kg^(-1))和阳性对照组(硝苯地平,50 mg·kg^(-1)),各20只,另设对照组。比较大鼠24 h尿蛋白(24 h UTP)、收缩压、舒张压、血清干扰素γ(IFN-γ)、白细胞介素12(IL-12)、白细胞介素10(IL-10)、白细胞介素33(IL-33)水平、仔鼠体质量、出生数量、死亡率、肾组织Th1淋巴细胞趋化因子C-X-C-基元受体3(CXCR3)、C-C趋化因子受体5(CCR5)及Th2淋巴细胞C-趋化因子C受体类型3(CCR3)mRNA和蛋白表达。结果 (1)24 h UTP、收缩压、舒张压、血清IFN-γ、IL-12、仔鼠出生数量、体质量和死亡率:与对照组比较,模型组均升高;与模型组比较,柚皮素低、高剂量组和阳性药组降低;与柚皮素低剂量组比较,高剂量组、阳性药组降低,阳性药组最低(P<0.05)。(2)IL-10、IL-33水平:模型组比对照组降低,与模型组比较,3个给药组均升高;柚皮素高剂量组与阳性药物组比柚皮素低剂量组高,且阳性药物组最高(P<0.05)。(3)CXCR3、CCR5 mRNA及蛋白水平:模型组比对照组增加;3个给药组均比模型组低;与柚皮素低剂量组比较,高剂量组和阳性药物组更低,阳性药物组最低(P<0.05)。(4)CCR3 mRNA及蛋白水平:模型组比对照组低;3个给药组均比模型组高;柚皮素高剂量组和阳性药物组比低剂量组高,阳性药物组最高(P<0.05)。结论 柚皮素可有效改善PIH大鼠症状,促进子代生长,可能与调节Th1/Th2平衡有关。

Objective To analyze the effects of naringin on improving symptoms and offspring growth of pregnancy induced hypertension(PIH)rats,and to explore the possible mechanisms.Methods Female rats were randomly divided into model group,naringin low-dose group(50 mg·kg^(-1)),naringin high-dose group(100 mg·kg^(-1)),and positive control group(nifedipine,50 mg·kg^(-1)),20 in each group.Meanwhile,a control group was also designed.The 24 hours'urine protein(24 h UTP),systolic blood pressure,diastolic blood pressure,the serum levels of interferonγ(IFN-γ),interleukin-12(IL-12),interleukin-10(IL-10),and interleukin-33(IL-33),body weight,birth number,mortality,Th1 lymphocyte chemokine C-X-C-receptor 3(CXCR3)in renal tissue,C-C chemokine receptor 5(CCR5),Th2 lymphocyte C-chemokine C receptor type 3(CCR3)mRNA and protein expression were compared.Results①The 24 h UTP,systolic blood pressure,diastolic blood pressure,serum IFN-γ,IL-12,birth number,body weight,and mortality were all increased in model group compared with control group.Compared with model group,those indexes in low dose,high dose and positive drug groups were decreased.Compared with naringin low-dose group,those indexes in high dose group and positive drug group were decreased,and positive drug group showed the lowest(P<0.05).②The levels of IL-10 and IL-33 in the model group were lower than those in the control group,and increased in all 3 administration groups compared with the model group.The levels of IL-10 and IL-33 in the naringin highdose group and positive drug group were higher than those in naringin low-dose group,and the positive drug group was the highest(P<0.05).③CXCR3 and CCR5 mRNA and protein levels were increased in model group compared with in control group.The 3 administration groups were lower than model group.Compared with the naringin low-dose group,the CXCR3 and CCR5 mRNA and protein levels of the high dose group and positive drug group were lower,and the positive drug group was the lowest(P<0.05).④CCR3 mRNA and protein levels in model group were lower than those in control group.The 3 drug administration groups were higher than the model group.The high dose group and positive drug group was higher than the low dose group,and the positive drug group was the highest(P<0.05).Conclusion Naringin can effectively improve the symptoms of PIH rats and promote the growth of their offspring,which may be related to the regulation of Th1/Th2 balance.