AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS Th...AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and healthyanimals.The classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the presentstudy.The hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify R-PK.RESULTS The apparent first-order absorption[Ka,（13.61±2.56）h<sup>-1</sup>,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h<sup>-1</sup>mL<sup>-1</sup>],maximum drug concentration[C<sub>max</sub>,（4.82±1.23）μg·mL<sup>-1</sup>]of serum TMP inRMSDS were increased markedly（P【0.05）compared with those[Ka=（5.41±1.91）h<sup>-1</sup>,AUC=（5.20±2.57）μg·h<sup>-1</sup>·mL<sup>-1</sup>,C<sub>max</sub>=（2.33±1.77）μg·mL<sup>-1</sup>]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h<sup>-1</sup>,β=（0.06±0.03）h<sup>-1</sup>,the apparent first-orderintercompartmental transfer rate constants[K<sub>10</sub>=（0.24±0.07）h<sup>-1</sup>,K<sub>12</sub>=（0.11±0.02）h<sup>-1</sup>,K<sub>21</sub>=（0.11±0.02）h<sup>-1</sup>]of serum TMP in RMSDS weredecreased significantly（P【0.01）comparedwith those[K<sub>10</sub>=（0.88±0.20）h<sup>-1</sup>,K<sub>12</sub>=（1.45±0.47）h<sup>-1</sup>,K<sub>21</sub>=（0.72±0.22）h<sup>-1</sup>]of HR.However,no apparent differences occurredbetween HR and RMSDS treated with SJZD.Theserum FA concentration and its AUC[（5.6690±2.3541）μg·h<sup>-1</sup>·mL<sup>-1</sup>] in RMBSS were also higherthan those[AUC=（2.7566±0.8232）μg·h<sup>-1</sup>·mL<sup>-1</sup>]of healthy rabbits（P【0.05）.The Ka（11.51±2.82）h<sup>-1</sup>,AUC（0.84±0.17）μg·h<sup>-1</sup>·mL<sup>-1</sup>of LW & SM-derived TMP in serum weremuch lower（P【0.05）than those[Ka=（19.58±4.14）h<sup>-1</sup>,AUC=（1.27±0.26）μg·h<sup>-1</sup>·mL<sup>-1</sup>]ofLW-derived TMP in serum after oral decoctions.CONCLUSION The SDS and blood stasissyndrome state could affect significantly thepharmacokinetic parameters of drugs and theabnormal SDS pharmacokinetic parameters couldbe normalized by SJZD.The combination ofChinese medicine in TCR could reciprocallyaffect the pharmacokinetic parameters of othercomponents absorbed into the systemiccirculation.These results support the S-and R-PK hypothesis.展开更多
[目的]探讨健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型糖尿病肾脏病(DKD)的临床疗效以及其对患者血清基质金属蛋白酶-9(MMP-9)、单核细胞趋化因子-1(MCP-1)和血管内皮生长因子(VEGF)水平的影响。[方法]选择沧州中西医结合医院2019...[目的]探讨健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型糖尿病肾脏病(DKD)的临床疗效以及其对患者血清基质金属蛋白酶-9(MMP-9)、单核细胞趋化因子-1(MCP-1)和血管内皮生长因子(VEGF)水平的影响。[方法]选择沧州中西医结合医院2019年1月—2021年5月纳入80例脾肾两虚夹瘀型DKD患者作为研究对象,采用随机数字表法分成观察组与对照组各40例。观察组给予健脾固肾化瘀方联合氯沙坦钾片治疗,对照组单用氯沙坦钾片治疗,连续治疗12周后观察两组临床疗效。治疗前后检测受试者血糖[空腹血糖(FPG)、餐后2 h血糖(2 h PG)和糖化血红蛋白(HbA1c)]、血脂[总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白胆固醇(LDL-C)]及肾功能指标[尿微量白蛋白/尿肌酐比值(UACR)、肌酐(SCr)和尿素氮(BUN)]。选用酶联免疫吸附法测定血清MMP-9、MCP-1和VEGF水平。并统计两组不良反应情况。[结果]观察组总有效率为92.50%(37/40),较对照组72.50%(29/40)有所提高(P<0.05)。两组治疗后FPG、2 h PG和HbA1c均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清TC、TG和LDL-C浓度均较治疗前下降(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后UAER和血清SCr、BUN水平均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清MMP-9水平均较治疗前升高(P<0.05),血清MCP-1、VEGF浓度均较治疗前下降(P<0.05);且治疗后,观察组对血清MMP-9水平的升高作用及对血清MCP-1、VEGF水平的降低作用较对照组更显著(P<0.01)。所有患者均无明显不良反应发生。[结论]应用健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型DKD能安全有效地上调患者MMP-9表达水平,下调MCP-1、VEGF表达水平,改善肾功能,整体疗效确切。展开更多
基金National Natural Science Foundation of China,No.398709323967086539570870 and 39100139.
文摘AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and healthyanimals.The classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the presentstudy.The hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify R-PK.RESULTS The apparent first-order absorption[Ka,（13.61±2.56）h<sup>-1</sup>,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h<sup>-1</sup>mL<sup>-1</sup>],maximum drug concentration[C<sub>max</sub>,（4.82±1.23）μg·mL<sup>-1</sup>]of serum TMP inRMSDS were increased markedly（P【0.05）compared with those[Ka=（5.41±1.91）h<sup>-1</sup>,AUC=（5.20±2.57）μg·h<sup>-1</sup>·mL<sup>-1</sup>,C<sub>max</sub>=（2.33±1.77）μg·mL<sup>-1</sup>]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h<sup>-1</sup>,β=（0.06±0.03）h<sup>-1</sup>,the apparent first-orderintercompartmental transfer rate constants[K<sub>10</sub>=（0.24±0.07）h<sup>-1</sup>,K<sub>12</sub>=（0.11±0.02）h<sup>-1</sup>,K<sub>21</sub>=（0.11±0.02）h<sup>-1</sup>]of serum TMP in RMSDS weredecreased significantly（P【0.01）comparedwith those[K<sub>10</sub>=（0.88±0.20）h<sup>-1</sup>,K<sub>12</sub>=（1.45±0.47）h<sup>-1</sup>,K<sub>21</sub>=（0.72±0.22）h<sup>-1</sup>]of HR.However,no apparent differences occurredbetween HR and RMSDS treated with SJZD.Theserum FA concentration and its AUC[（5.6690±2.3541）μg·h<sup>-1</sup>·mL<sup>-1</sup>] in RMBSS were also higherthan those[AUC=（2.7566±0.8232）μg·h<sup>-1</sup>·mL<sup>-1</sup>]of healthy rabbits（P【0.05）.The Ka（11.51±2.82）h<sup>-1</sup>,AUC（0.84±0.17）μg·h<sup>-1</sup>·mL<sup>-1</sup>of LW & SM-derived TMP in serum weremuch lower（P【0.05）than those[Ka=（19.58±4.14）h<sup>-1</sup>,AUC=（1.27±0.26）μg·h<sup>-1</sup>·mL<sup>-1</sup>]ofLW-derived TMP in serum after oral decoctions.CONCLUSION The SDS and blood stasissyndrome state could affect significantly thepharmacokinetic parameters of drugs and theabnormal SDS pharmacokinetic parameters couldbe normalized by SJZD.The combination ofChinese medicine in TCR could reciprocallyaffect the pharmacokinetic parameters of othercomponents absorbed into the systemiccirculation.These results support the S-and R-PK hypothesis.
文摘[目的]探讨健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型糖尿病肾脏病(DKD)的临床疗效以及其对患者血清基质金属蛋白酶-9(MMP-9)、单核细胞趋化因子-1(MCP-1)和血管内皮生长因子(VEGF)水平的影响。[方法]选择沧州中西医结合医院2019年1月—2021年5月纳入80例脾肾两虚夹瘀型DKD患者作为研究对象,采用随机数字表法分成观察组与对照组各40例。观察组给予健脾固肾化瘀方联合氯沙坦钾片治疗,对照组单用氯沙坦钾片治疗,连续治疗12周后观察两组临床疗效。治疗前后检测受试者血糖[空腹血糖(FPG)、餐后2 h血糖(2 h PG)和糖化血红蛋白(HbA1c)]、血脂[总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白胆固醇(LDL-C)]及肾功能指标[尿微量白蛋白/尿肌酐比值(UACR)、肌酐(SCr)和尿素氮(BUN)]。选用酶联免疫吸附法测定血清MMP-9、MCP-1和VEGF水平。并统计两组不良反应情况。[结果]观察组总有效率为92.50%(37/40),较对照组72.50%(29/40)有所提高(P<0.05)。两组治疗后FPG、2 h PG和HbA1c均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清TC、TG和LDL-C浓度均较治疗前下降(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后UAER和血清SCr、BUN水平均较治疗前降低(P<0.05),且均以观察组的改善更显著(P<0.01)。两组治疗后血清MMP-9水平均较治疗前升高(P<0.05),血清MCP-1、VEGF浓度均较治疗前下降(P<0.05);且治疗后,观察组对血清MMP-9水平的升高作用及对血清MCP-1、VEGF水平的降低作用较对照组更显著(P<0.01)。所有患者均无明显不良反应发生。[结论]应用健脾固肾化瘀方联合氯沙坦钾片治疗脾肾两虚夹瘀型DKD能安全有效地上调患者MMP-9表达水平,下调MCP-1、VEGF表达水平,改善肾功能,整体疗效确切。
