首页|脉血康胶囊减轻IgA肾病大鼠肾纤维化的作用和机制

脉血康胶囊减轻IgA肾病大鼠肾纤维化的作用和机制

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目的 探讨脉血康胶囊对免疫球蛋白A肾病(IgAN)大鼠肾纤维化的改善及对Janus酪氨酸蛋白激酶2(JAK2)/信号转导与转录激活因子家族3(STAT3)信号通路的抑制作用.方法 用600 mg·kg-1改良的牛血清白蛋白(BSA)+脂多糖0.2 mL(LPS)+四氯化碳(CC14)0.1 mL方案建立IgAN大鼠模型.将55只SD大鼠随机分为空白对照组(蒸馏水+0.9%NaCl)、模型组(IgAN模型)、阳性对照组(建模后灌胃给予替米沙坦片10 mg·kg-1)和低、中、高3个剂量实验组(建模后灌胃给予脉血康胶囊16、44和84ATU·kg-1).检测大鼠24 h尿蛋白;用全自动生化分析仪测定血肌酸酐(Scr)、血尿素氮(BUN)、谷丙转氨酶(GPT)、谷草转氨酶(GOT)水平;用苏木精-伊红(HE)染色法观察肾组织形态;用免疫荧光法检测IgA在大鼠肾中的沉积;用蛋白质印迹法检测肾组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、JAK2、STAT3、磷酸化STAT3(p-STAT3)蛋白的表达.结果 空白对照组、模型组、阳性对照组与高剂量实验组的血 Scr 分别为(41.42±2.30)、(59.82±5.36)、(50.28±3.18)和(50.47±7.19)μmol·L-1,24 h 尿蛋白分别为(2.35±1.21)、(11.62±3.45)、(5.01±4.36)和(8.14±4.19)mg·d-1,α-SMA蛋白相对表达水平分别为0.48±0.10、1.00±0.00、0.71±0.13 和 0.57±0.22,TGF-β1 蛋白相对表达水平分别为 0.54±0.93、1.00±0.00、0.73±0.33 和 0.51±0.31,JAK2 蛋白相对表达水平分别为 0.36±0.22、1.00±0.00、0.82±0.36 和 0.57±0.28,p-STAT3/STAT3 分别为 0.40±0.19、1.00±0.00、0.46±0.18 和 0.31±0.18.模型组的上述指标与空白对照组比较,在统计学上差异均有统计学意义(均P<0.05),阳性对照组和高剂量实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P<0.05).结论 脉血康胶囊可能通过抑制JAK2/STAT3信号通路的激活减轻IgAN大鼠肾纤维化水平,保护肾功能.
Effects and mechanism of Maixuekang capsule on reducing renal fibrosis in IgA nephropathy rats
Objective To explore the effect of Maixuekang capsules on renal fibrosis and inhibition of Janus tyrosine protein kinase 2(JAK2)/signal transducer and activator of transcription family 3(STAT3)signal pathway in rats with immunoglobulin A nephropathy(IgAN).Methods The rat model of IgAN was established by modified 600 mg·kg-1 BSA+LPS 2 mL+CCL4 0.1 mL scheme,and the 24-hour urinary protein was detected.Fifty-five SD rats were randomly divided into 6 groups:Blank control group(distilled water+0.9%NaCl),model group(IgAN model),positive control group(10 mg·kg-1 telmisartan tablets after modeling),experimental-L,-M,-H groups(16,44,84 ATU·kg-1 Maixuekang capsules after modeling).The levels of serum creatinine(Scr),blood urea nitrogen(BUN),glutamic pyruvic transaminase(GPT)and glutamic oxalacetic transaminase(GOT)were determined by automatic biochemical analyzer.The morphology of kidney was observed by hematoxylin-eosin(HE)staining,and the deposition of IgA in rat kidney was detected by immunofluorescence.The expressions of α-SMA,TGF-β1,JAK2,STAT3 and P-STAT3 in renal tissue were detected by Western blot.Results The blood Scr of blank control group,model group,positive control and experimental-H groups were(41.42±2.30),(59.82±5.36),(50.28±3.18)and(50.47±7.19)μ mol·L-1,respectively;the 24-hour urinary protein were(2.35±1.21),(11.62±3.45),(5.01±4.36)and(8.14±4.19)mg·d-1,respectively;the relative expression of α-SMA protein were 0.48±0.10,1.00±0.00,0.71±0.13 and 0.57±0.22,respectively;the relative expression of TGF-β1 protein were 0.54±0.93,1.00±0.00,0.73±0.33 and 0.51±0.31,respectively;the relative expression of JAK2 protein were 0.36±0.22,1.00±0.00,0.82±0.36 and 0.57±0.28,respectively;p-STAT3/STAT3 were 0.40±0.19,1.00±0.00,0.46±0.18 and 0.31±0.18,respectively.Compared with the blank control group,the differences of above indexes in the model group were statistically significant(all P<0.05).Compared with the model group,the differences of above indexes in the positive control and experimental-H groups were statistically significant(all P<0.05).Conclusion Maixuekang capsules may reduce the level of renal fibrosis and protect renal function in rats with IgAN by inhibiting the activation of JAK2/STAT3 signal pathway.

Maixuekang capsulesimmunoglobulin A nephropathyfibrosisJanus tyrosine protein kinase 2/signal transducer and activator of transcription family 3

陆瑾瑜、丁爱霞、陆晨

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新疆医科大学第一附属医院肾脏疾病中心,新疆维吾尔自治区乌鲁木齐 830054

新疆大学生命科学与技术学院,新疆维吾尔自治区乌鲁木齐 830046

脉血康胶囊 免疫球蛋白A肾病 纤维化 Janus酪氨酸蛋白激酶2/信号转导与转录激活因子家族3

科技创新领军人才基金资助项目

2022TSYCLJ0022

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(13)
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