雷公藤多苷对盐敏感性高血压小鼠肾损害的保护作用

Protective effect of multi-glycoside of Tripterygium wilfordii Hook. F. on salt-sensitive hypertension-induced renal injury in mice

目的阐明雷公藤多苷(GTW)对盐敏感性高血压所导致的肾损害的保护作用及其机制。方法用切除左肾,皮下植入醋酸脱氧皮质酮(DOCA)和饮用盐水的方法制备盐敏感性高血压小鼠模型。实验小鼠共分为对照组、模型组、实验组。对照组予以切除左肾,0.9%NaCl灌胃;模型组予以DOCA-盐制备模型,0.9%Na Cl灌胃;实验组予以DOCA-盐制备模型,GTW溶液23 mg·kg^(-1)·d^(-1)。3组小鼠每日灌胃2次,连续5周。比较3组小鼠24 h尿白蛋白和尿8-异构前列腺素排泄水平、肌酸酐清除率、肾组织病理学改变,以及单核/巨噬细胞浸润程度。结果治疗后,实验组、对照组和模型组的尿白蛋白排泄量分别为(22.49±3.97),(5.70±0.98)和(48.75±4.49)μg·24 h^(-1),尿8-异构前列腺素排泄量分别为(1.84±0.30),(0.42±0.08)和(3.07±0.47)ng·24 h^(-1),肌酸酐清除率分别为(245.02±27.86),(336.53±25.99)和(133.76±18.18)mL·24 h^(-1),肾小球硬化指数分别为(0.27±0.06),(0.09±0.04)和(0.64±0.10),肾小管间质损伤分数分别为(1.25±0.29),(0.34±0.16)和(3.10±0.46),肾F4/80阳性细胞的数量分别为(18.84±5.36),(9.80±1.72)和(63.00±9.13)cell·mm^(-2),模型组的上述指标与实验组和对照组比较,差异均有统计学意义(均P<0.05)。结论 GTW通过抑制单核/巨噬细胞浸润为主的炎症反应,从而实现其对DOCA-盐高血压所导致的肾损害的保护作用。

Objective To clarify the protective effect of multi-glycoside of Tripterygium wilfordii Hook. F.（ GTW） on salt-sensitive hypertension-induced renal injury in mice. Methods To establish salt-sensitive hypertension model,the mice were subjected to uninephrectomy and deoxycorticosterone acetate（ DOCA）-salt treatment. The mice were assigned into control group,model group and test group. The control group treated by uninephrectomy was gavaged with 0. 9% NaCl; the model group treated by DOCA-salt was gavaged with 0. 9% NaCl; the test group treated by DOCA-salt was gavaged with GTW 23 mg·kg^-1·d^-1.All of the three groups were continuously gavaged twice a day for 5 weeks. The excretion of urinary albumin and 8-isoprostane,creatinine clearance,the changes in renal pathology and monocyte/macrophage infiltration were compared among the three groups. Results After treatment,the excretion of urinary albumin for the test group,control groupand model group were（ 22. 49 ± 3. 97）,（ 5. 70 ± 0. 98） and（ 48. 75 ± 4. 49） μg·24 h^-1; the excretion of 8-isoprostane for the three groups were（ 1. 84 ± 0. 30）,（ 0. 42 ± 0. 08） and（ 3. 07 ± 0. 47） ng·24 h^-1; the creatinine clearance for the three groups were（ 245. 02 ± 27. 86）,（ 336. 53 ± 25. 99） and（ 133. 76 ± 18. 18） mL·24 h^-1; the glomerulosclerosis index for the three groups were（ 0. 27 ± 0. 06）,（ 0. 09 ± 0. 04） and（ 0. 64 ± 0. 10）; the tubulointerstitial injury score for the three groups were（ 1. 25 ± 0. 29）,（ 0. 34 ± 0. 16） and（ 3. 10 ± 0. 46）; the renal F4/80 positive cells for the three groups were（ 18. 84 ± 5. 36）,（ 9. 80 ± 1. 72） and（ 63. 00 ± 9. 13） cell·mm^（-2）. Compared with the test group and the control group,the differences in all of the parameters described above in the model group were statistically significant（ all P 0. 05）. Conclusion GTW could ameliorate renal injury in DOCA-salt hypertension via inhibiting monocyte/macrophage infiltration.