摘要目的 探讨山茱萸总甙治疗IgA肾病(IgAN)的作用机制.方法 将50只SD大鼠按随机数字表法随机分为正常对照组、IgAN模型组、地塞米松组、山茱萸总甙高剂量组、山茱萸总甙低剂量组.采用口服牛血清清蛋白(BSA)皮下注射四氯化碳(CCl4)、蓖麻油和尾静脉注射脂多糖(LPS)方法建立IgAN大鼠模型.观察给药10周后大鼠各时相尿红细胞计数、24h尿蛋白定量(24 h-UTP)变化,造模成功后地塞米松组、山茱萸总甙组再给药8周,然后检测不同组大鼠尿液、血清白细胞介素-18(IL-18)、转化生长因子-β1(TGF-β1)水平及肾组织病理变化.结果 与IgAN模型组相比,18周末各组大鼠24 h-UTP均有所下降,其中山茱萸总甙高剂量组下降最为显著,差异有统计学意义[(8.8 ±3.2) mg/24 h比(35.2±5.6) mg/24 h,t=10.511,P=0.000];山茱萸总甙高剂量组尿红细胞计数明显减少,差异有统计学意义[(148.2±41.8)个/μL比(683.8±24.6)个/μL,t=10.909,P=0.000];地塞米松组尿中红细胞计数有轻微下降,但差异无统计学意义(t=3.014,P=0.061).与正常对照组比较,IgAN模型组大鼠尿液、血清中IL-18、TGF-β1水平均明显升高,差异均有统计学意义(均P＜0.05).与IgAN模型组比较,山茱萸总甙高剂量组大鼠尿液、血清中IL-18、TGF-β1均明显减少,差异均有统计学意义(均P＜0.05);肾组织病理变化与IgAN模型组相比,山茱萸总甙高剂量组在M1T1/2上,所占比例明显减少.结论 山茱萸总甙延缓肾损害的作用机制可能与下调IL-18、TGF-β1的表达、减轻肾组织IgA沉积有关,山茱萸总甙可以抑制大鼠肾系膜细胞增生、肾小管萎缩及间质纤维化等,对IgAN大鼠有一定程度的治疗作用.

abstractsObjective To study the mechanism of Comus officinalis glucosides treatment of IgA nephropathy.Methods Fifty SD rats were randomly divided into the control group,the IgAN model group,the Dexamethasone group,the Comus officinalis glucosides in the high-dose group and in the low-dose group.The IgA nephropathy rat models were established by feeding bovine serum albumin (BSA),subcutaneous injection of carbon tetrachloride (CCl4),castor oil and injecting tail vein with lipopolysaccharide (LPS).After 10 weeks of administration,the urine red blood cell count,UTP in each phase were observed after the rat models were successfully established.Then Dexamethasone group and Comus officinalis total glucoside group were given medicine for 8 weeks,and urine or serum content of interleukin-18 (IL-18),transforming growth factor-β1 (TGF-β1) in different groups of rats and pathological changes of kidneys were detected.Results Compared with the IgAN model group,24 h-UTP of each group decreased and Comus officinalis glucosides in high-dose group decreased extraordinary [(8.8 ± 3.2) mg/24 h vs.(35.2 ± 5.6) mg/24 h,t =10.511,P =0.000].Compared with the IgAN model group,urine red blood cell count decreased significantly in the high-dose group of Comus officinalis glucosides[(148.2 ±41.8) 个/μL vs.(683.8 ±24.6) 个/μL,t =10.909,P =0.000];but urine red blood cell count in the Dexamethasone group declined slightly,but there was no statistically significant difference(t =3.014,P =0.061).Compared with the control group,IL-18,TGF-β1,and rat urine or serum of IgAN model group was significantly elevated (all P ＜ 0.05).Compared with IgAN model group,IL-18,TGF-β1 of the high-dose group of Comus officinalis glucosides in rats urine or serum decreased significantly(all P ＜ 0.05).The effect of high-dose group of Comus officinalis glucosides on the pathological changes in kidney tissues was the most significant.Conclusions The mechanism of Comus officinalis glucosides may postpone renal lesion that can be associated with the down-regulation of the expression of IL-18,TGF-β1 and the inhibition of the deposition of IgA in the renal tissue.Comus officinalis glucosides can inhibit the proliferation of mesangial cells,tubular atrophy and interstitial fibrosis in IgAN rats,which has a certain curative effect on IgAN rats.