基于IL-6/JAK2/STAT3通路探讨化浊解毒方对5/6肾切除大鼠肾纤维化的影响OA
Exploration on the Effects of Huazhuo Jiedu Prescription on Renal Fibrosis in 5/6 Nephrectomized Rats Based on the IL-6/JAK2/STAT3 Signaling Pathway
目的 观察化浊解毒方对慢性肾衰竭(CRF)大鼠肾脏损伤及IL-6/JAK2/STAT3通路的影响,探讨其延缓肾纤维化的作用机制.方法 61只雄性SD大鼠随机分为正常组10只和造模组51只,采用5/6肾切除法构建CRF模型,将造模成功的大鼠随机分为模型组、氯沙坦钾组(4.5 mg/kg)和化浊解毒方低、中、高剂量组(1.175、2.350、4.700 g/kg),每组8只,各给药组分别予相应药物灌胃,每日1次,连续8周.HE和Masson染色观察肾组织形态,ELISA检测血清肿瘤坏死因子(TNF-α)、白细胞介素(IL)-6、单核细胞趋化蛋白-1(MCP-1)含量,Western blot检测肾组织Ⅰ型胶原蛋白(Col-Ⅰ)、Ⅲ型胶原蛋白(Col-Ⅲ)、α平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、Bcl-2、Bax、裂解型胱天蛋白酶3(Cleaved Caspase-3)、IL-6、Janus激酶2(JAK2)、信号转导与转录激活因子3(STAT3)、p-JAK2、p-STAT3、蛋白表达,TUNEL染色评估肾组织细胞凋亡情况,免疫组化染色检测Col-Ⅰ、Col-Ⅲ、IL-6、p-JAK2、p-STAT3阳性表达.结果 与正常组比较,模型组大鼠肾组织结构破坏明显,纤维化程度加重,血清TNF-α、IL-6、MCP-1含量和肾组织Col-Ⅰ、Col-Ⅲ、α-SMA、TGF-β1、Bax、Cleaved Caspase-3、IL-6、p-JAK2、p-STAT3蛋白表达显著升高(P<0.01),Bcl-2蛋白表达显著降低(P<0.01);与模型组比较,各给药组肾组织损伤不同程度减轻,胶原纤维面积减少,化浊解毒方中、高剂量组和氯沙坦钾组大鼠血清TNF-α、IL-6、MCP-1含量及肾组织Col-Ⅰ、Col-Ⅲ、α-SMA、TGF-β1、Bax、Cleaved Caspase-3、IL-6、p-JAK2、p-STAT3蛋白表达显著降低(P<0.05,P<0.01),Bcl-2蛋白表达显著升高(P<0.05,P<0.01).免疫组化Col-Ⅰ、Col-Ⅲ、IL-6、p-JAK2、p-STAT3表达结果与Western blot一致.结论 化浊解毒方可能通过调控IL-6/JAK2/STAT3通路,抑制炎症反应,减轻细胞凋亡,从而减轻肾脏损伤,延缓肾纤维化进展.
Objective To investigate the effects of Huazhuo Jiedu Prescription on renal injury and the IL-6/JAK2/STAT3 pathway in rats with chronic renal failure(CRF);To explore its mechanism in delaying renal fibrosis.Methods Totally 61 male SD rats were randomly divided into a normal group(n=10)and a modeling group(n=51).CRF model was established via 5/6 nephrectomy.The successful modeled rats were randomly divided into model group,losartan potassium group(4.5 mg/kg)and Huazhuo Jiedu Prescription low-,medium-and high-dosage groups(1.175,2.350 and 4.700 g/kg),with 8 rats in each group.Each treatment group was given corresponding drugs by gavage once a day for 8 weeks.Renal histopathology was examined using HE and Masson staining,serum contents of TNF-α,IL-6 and MCP-1 were detected by ELISA,the expressions of Col-Ⅰ,Col-Ⅲ,α-SMA,TGF-β1,Bcl-2,Bax,Cleaved Caspase-3,IL-6,JAK2,STAT3,p-JAK2,p-STAT3 were detected by Western blot,renal apoptosis was assessed using TUNEL staining,the positive expressions of Col-Ⅰ,Col-Ⅲ,IL-6,p-JAK2 and p-STAT3 were detected by immunohistochemistry.Results Compared with the normal group,the renal tissue structure of rats in the model group exhibited significant damage,with an aggravated degree of fibrosis,the contents of TNF-α,IL-6 and MCP-1 in serum and the protein expressions of Col-Ⅰ,Col-Ⅲ,α-SMA,TGF-β1,Bax,Cleaved Caspase-3,IL-6,p-JAK2 and p-STAT3 in renal tissue significantly increased(P<0.01),while the protein expression of Bcl-2 significantly decreased(P<0.01).Compared with the model group,the renal tissue damage was alleviated to varying degrees,and the area of collagen fibers decreased in each administration group,the contents of TNF-α,IL-6 and MCP-1 in serum and the protein expressions of Col-Ⅰ,Col-Ⅲ,α-SMA,TGF-β1,Bax,Cleaved Caspase-3,IL-6,p-JAK2 and p-STAT3 in renal tissue of rats in Huazhuo Jiedu Prescription medium-and high-dosage groups and losartan potassium groups significantly decreased(P<0.05,P<0.01),and the protein expression of Bcl-2 significantly increased(P<0.05,P<0.01).The expression of Col-Ⅰ,Col-Ⅲ,IL-6,p-JAK2 and p-STAT3 were consistent with Western blot.Conclusion Huazhuo Jiedu Prescription may alleviate renal injury and delay renal fibrosis by regulating the IL-6/JAK2/STAT3 pathway,inhibiting inflammation,and modulating apoptosis.
邓婉莹;郑琳琳;高卉;高芸慧;邹佳颖;边东;冯忖;魏晓娜
河北中医药大学研究生学院,河北 石家庄 050091||河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011||河北省中医院,河北 石家庄 050000河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011||河北省中医院,河北 石家庄 050000河北中医药大学研究生学院,河北 石家庄 050091||河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011河北中医药大学研究生学院,河北 石家庄 050091||河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011||河北省中医院,河北 石家庄 050000河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011||河北省中医院,河北 石家庄 050000河北中医药大学研究生学院,河北 石家庄 050091||河北省脾肾病证中医治疗技术创新中心,河北 石家庄 050000||河北省浊毒证重点实验室,河北 石家庄 050011||河北省中医院,河北 石家庄 050000
医药卫生
化浊解毒方慢性肾衰竭肾纤维化凋亡IL-6/JAK2/STAT3通路大鼠
Huazhuo Jiedu Prescriptionchronic renal failurerenal fibrosisapoptosisIL-6/JAK2/STAT3 pathwayrats
《中国中医药信息杂志》 2026 (6)
82-89,8
河北省自然科学基金(H2023423067)河北省中医药管理局科研计划(2025206)
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