柚皮苷在大鼠在体单向肠灌流模型上的吸收特征研究

Study on the Absorption Characteristics of Naringin in situ Single-pass Intestinal Perfusion Model of Rats

目的:研究柚皮苷在大鼠在体单向肠灌流模型上的吸收特征。方法:建立检测大鼠肠道灌流样品中柚皮苷、柚皮素含量的超高效液相色谱法,采用大鼠在体单向肠灌流模型,考察柚皮苷(10μmol/L)的肠道(十二指肠、空肠、回肠、结肠)吸收及代谢特征[表观渗透系数(P_(eff))、吸收率、代谢率]。结果:柚皮苷、柚皮素在1.25~40、1.25~40μmol/L浓度范围内线性关系良好(R^2=0.999 4、0.996 6),检测限分别为0.5、0.4μmol/L,定量限均为1.25μmol/L,日内、日间精密度和回收率及在HBSS液及其小肠、结肠灌流液中的稳定性均符合相关要求。柚皮苷在大鼠十二指肠、空肠、回肠、结肠中的Peff分别为(0.28±0.19)、(0.71±0.17)、(0.30±0.02)、(0.59±0.19)(n=6),差异无统计学意义(P>0.05);吸收率分别为(2.90±2.14)%、(6.38±3.61)%、(3.69±0.56)%、(6.64±2.12)%(n=6);柚皮苷在大鼠4个肠段均可被代谢为柚皮素,代谢率分别为(2.98±1.51)%、(2.53±1.31)%、(2.24±1.33)%、(0.70±0.20)%(n=6)。柚皮苷在十二指肠中的吸收率最低,代谢率最高,与结肠比较差异均有统计学意义(P<0.05)。结论:柚皮苷在大鼠肠道渗透性差、吸收不佳;柚皮苷在大鼠肠道无特定吸收部位,在小肠和结肠中均可被代谢为柚皮素,但小肠的代谢率明显高于结肠。

OBJECTIVE：To study absorption characteristics of naringin in situ single-pass intestinal perfusion model of rats.METHODS：UPLC method was established for the content determination of naringin and naringenin in intestinal perfusion samples of rats. The in situ single-pass intestinal perfusion model of rats was adopted to investigate intestinal（duodenum,jejunum,ileum and colon） absorption and metabolic characteristics [apparent permeability coefficient（P_（eff））,absorptivity,metabolic rate] of naringin（10 μ mol/L）. RESULTS：The linear range of naringin and naringenin were 1.25-40,1.25-40 μ mol/L（R^2=0.999 4,0.996 6）. The detection limit were 0.5,0.4 μmol/L,and limit of quantitation were all 1.25 μmol/L. Precision of inter-day and intra-day,recovery and stability in HBSS solution,perfusion fluid of small intestine and colon were all in line with the standard.Peffof naringin in duodenum,jejunum,ileum and colon of rats were（0.28±0.19）,（0.71±0.17）,（0.30±0.02）,（0.59±0.19）（n=6）,without statistical significance（P〈0.05）. Absorptivities were（2.90±2.14）%,（6.38±3.61）%,（3.69±0.56）%,（6.64±2.12）%（n=6）. Naringin could be metabolized to naringenin in 4 intestinal segments of rats,with metabolic rate of（2.98 ±1.51）%,（2.53 ± 1.31）%,（2.24 ± 1.33）%,（0.70 ± 0.20）%（n=6）. The lowest absorptivity and the highest metabolic rate of naringin were occurred in the duodenum,there were statistical significance compared with colon（P〈0.05）. CONCLUSIONS：Naringin shows poor permeability and poor absorption in the intestinal tract of rats. There was no specific absorption site in the rat＇s intestines for naringenin;naringin could be metabolized to naringenin in small intestine and colon,but metabolic rate of naringin in small intestine is higher than in colon.