| 古丽鲜· 吐尔洪,阿布力米提·阿木提,李 敏,坤多姿·玉山江,李光玉.激素治疗IgA肾病大鼠对骨密度和TLR4信号通路的影响[J].,2024,(5):836-840 |
| 激素治疗IgA肾病大鼠对骨密度和TLR4信号通路的影响 |
| Study on Bone Density and TLR4 Signaling Pathway in IgA Nephropathy Rat Treated with Steroids |
| 投稿时间：2023-12-01 修订日期：2023-12-23 |
| DOI：10.13241/j.cnki.pmb.2024.05.006 |
| 中文关键词: 糖皮质激素 IgA肾病 骨密度 TLR4信号通路 骨小梁 |
| 英文关键词: Glucocorticoid IgA nephropathy Bone density TLR4 signaling pathway Bone trabecular |
| 基金项目:新疆少数民族科技人才特殊培养计划科研项目(2021D03023) |
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| 中文摘要: |
| 摘要 目的：探讨糖皮质激素治疗IgA肾病大鼠对骨密度变化和TLR4信号通路活性的影响。方法：选择5月龄SPF级SD雄性大鼠共60只，平均体重185 g，随机分为4组，分别为对照组、非激素组、激素低剂量组和高剂量组，每组各15只。采用牛血清白蛋白灌胃+ CCl4和蓖麻油皮下注射+脂多糖尾静脉注射法复制IgA肾病模型，周期为9周。非激素组采用盐酸贝那普利片（1.041 mg/kg/d），激素低剂量组采用甲泼尼龙15 mg/kg/d，高剂量组采用甲泼尼龙30 mg/kg/d，持续灌胃10周至实验结束。检测各组尿红细胞计数和24h尿蛋白定量，血清肌酐和尿素氮，采用双能 X 射线吸收法测量股骨的骨密度值，Micro-CT骨扫描并计算骨小梁微观结构参数，包括骨小梁数、骨小梁厚度和体积分数，Western blot法检测骨组织中Toll 样受体 4（TLR4）、髓样分化因子（MyD88）和核因子-κB（NF-κB）蛋白。结果：各组大鼠均存活至实验结束，激素低剂量组和高剂量组治疗后尿红细胞计数、24 h尿蛋白定量、血清肌酐和尿素氮均显著降低，骨密度值、骨小梁数、骨小梁厚度和体积分数也显著下降，但是TLR4、MyD88和NF-κB蛋白表达量明显升高（P＜0.05）。结论：糖皮质激素治疗IgA肾病能够改善临床症状和肾功能，但同时降低了骨密度和改变了骨小梁结构，可能与骨组织TLR4信号通路的异常激活有关。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effects of glucocorticoid treatment on bone density change and TLR4 signaling pathway activity in IgA nephropathy rats. Methods: 60 male SD rats of SPF grade, 5-month old, mean weight of 185g were selected and randomly divided into 4 groups: control group, non-hormone group, low-dose hormone group, and high-dose hormone group, with 15 rats in each group. The IgA nephropathy model was replicated by gavage of bovine serum albumin+ subcutaneous injection of CCl4 and castor oil+tail vein injection of lipopolysaccharide, with 9 weeks. The non-hormone group received benazepril hydrochloride tablets (1.041 mg/kg/d), the low-dose hormone group received methylprednisolone 15 mg/kg/d, and the high-dose hormone group received methylprednisolone 30 mg/kg/d, continuously administered by gavage for 10 weeks until the end of experiment. Then to detect urine red blood cell count and 24-hour urine protein quantification, serum creatinine and urea nitrogen in each group. Bone density of femur was measured using dual energy X-ray absorption method. Bone trabecular microstructure parameters were scanned and calculated by micro-CT, including bone trabecular number, bone trabecular thickness, and volume fraction. Western blot method was to detect Toll like receptor 4 (TLR4), myeloid differentiation factor (MyD88), and nuclear factor-κB (NF-κB) proteins in bone tissues. Results: All rats survived until the end of experiment. After treatment, the low-dose and high-dose hormone groups significantly reduced urinary red blood cell count, 24-hour urine protein quantification, serum creatinine, and urea nitrogen, as well as bone density, trabecular number, trabecular thickness, and volume fraction. However, TLR4, MyD88, and NF-κB proteins significantly increased (P<0.05). Conclusion: Glucocorticoid therapy for IgA nephropathy can improve clinical symptom and renal function, but at the same time, it reduces bone density and alters bone trabecular structure, which may be related to abnormal activation of TLR4 signaling pathway in bone tissues. |
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