基于“有故无殒”思想的雷公藤对肾小管S1和S2段保护与损伤的“双向作用”

Differences in the renal toxicity of Tripterygium wilfordii Hook.f.on acute renal failure model rats with tubular S1 and S2 damaged:based on "symptom-based prescription theory"

目的基于"有故无殒"思想,研究不同剂量的雷公藤对肾小管S1段和S2段损伤急性肾衰模型大鼠肾毒性的差异。方法将雄性SD大鼠48只,按体重大小编号,按随机数字表法将其分为6组,每组8只,分别为空白组(N组)、模型组(M组)、模型组+1倍剂量雷公藤提取物(TWHF)组(MD1组)、模型组+2倍剂量TWHF组(MD2组)、模型组+4倍剂量TWHF组(MD3组)、模型组+8倍剂量TWHF组(MD4组)。采用氯化镉造模,4个TWHF剂量组按照3.13、6.25、13.5、27.0 g生药/kg给药。观察TWHF对肾小管S1段和S2段损伤大鼠的一般生长状态、肾脏脏器指数、血清生化指标(BUN、CREA、K+、Na+、Ca2+、Cl-)、肾脏组织病理改变的影响。结果与N组比较,M组体重下降,尿量减少,肾脏脏器指数升高,BUN、CREA、K+浓度显著增高,Na+、Ca2+浓度明显降低,肾脏病理可见肾小管损伤。与M组比较,MD1、MD2组体重早期稍增长,尿量无明显改变,肾脏脏器指数有所下降,MD1组BUN降低,CREA、K+浓度明显降低;MD2组BUN、K+浓度无明显改变,CREA水平显著降低,Ca2+浓度显著升高,MD1、MD2组肾脏病理损伤有所减轻。与M组比较,MD3、MD4组体重下降更为明显,每组各出现1例小鼠死亡,尿量明显减少,肾脏脏器指数进一步增高,BUN、CREA、K+、Ca2+进一步增高,Na+浓度明显降低,肾脏病理损伤进一步加重。结论低剂量TWHF在模型大鼠上表现出改善BUN、CREA、血清高K+和低Na+水平的保护作用,肾脏病理改变减轻,但高剂量时反而加重M组大鼠肾损伤。这证实了"有故无殒"的思想,因而临床用药时,需要把握不同病理状态的雷公藤的量-毒效差异。

Objective Based on the ＂symptom-based prescription theory＂, to study the differences in the renal toxicity of Tripterygium wilfordii Hook.f. on normal and acute renal failure model rats with tubular S1 and S2 damaged. Methods 48 male SD rats were randomly divided into 6 groups, which were normal group （N group）, model group （M group）, model ＋1 times dose TWHF group （MD1 group）, model ＋2 times dose TWHF group （MD2 group）, model ＋4 times dose TWHF group （MD3 group）, model ＋8 times dose TWHF group （MD4 group） respectively. The models were made by cadmium chloride, 4 TWHF dose groups were administered in 3.13, 6.25, 13.5, 27.0 g crude drug/kg（ The general growth status, organ/bady coefficients, serum biochemical indexes and renal pathological changes were used to investigate the influence of the TWHF on physiological and pathological state. Results Compared with the N group, body weight Of the rats and urine volume decreased, kidney organ index increased; BUN, CREA, K^＋ concentrationswere increased significantly, Na^＋, Ca^2＋ concentrations were decreased significantly, pathological examination revealed renal tubular injury in M group. Compared with M group, body weight of the rats slightly increased at the early stage, urine volume did not change significantly, kidney index decreased in MD1 and MD2 groups. BUN was decreased, CREA and K^＋ were decreased significantly in MD1 group; BUN and K^＋ were no significant change,CREA was significantly decreased, Ca^2＋ concentration was significantly increased in MD2 group, the damage of kidney pathology had been improved in MD1 and MD2 groups. Compared with M group, body weight of the rats decreased significantly in MD3 and MD4 groups, 1 rat death in each group, urine volume was decreased significantly, kidney index was increased significantly, BUN, CREA, K^＋ and Ca^2＋ were increased further, Na^＋ concentration was decreased significantly, the renal pathological damage was aggravated. Conclusion Low-doses TWHF plays a protective role by improved BUN, CREA, serum high K^＋ , low Na^＋ levels and the pathological change of kidney in the model rats. However, high-dose TWHF aggravated renal injury of the rats. This phenomenon has proved ＂symptom-based prescription theory＂. Therefore, it is necessary to grasp the different pathological state of the made the symptom-based prescription.