胸腺肽α1对皮肤移植小鼠免疫功能的影响

The Effects of Thymosin α1 on Immune Functionof Mice after Skin Transplantation

中文关键词:  胸腺肽α1 环孢素A 皮肤移植 免疫耐受 免疫调节

英文关键词:Thymosin α1 Cyclosporin A Skin transplantation Immune tolerance Immune regulation

中文摘要:

      目的 本研究拟通过建立C57-BABL/c小鼠同种异体皮肤移植模型,观察胸腺肽α1（Tα1）对皮肤移植小鼠免疫功能的影响,同时探讨Tα1在体内诱导移植免疫耐受的机制。方法 取80只C57小鼠作为供体，80只BABL/c小鼠作为受体，建立C57-BABL/c小鼠同种异体皮肤移植模型，将移植术后的受体小鼠分为4组：A组，对照组（移植后不给予任何药物，n=20）；B组，环孢素A（CsA）治疗组（移植后给予CsA 10 mg/kg，n=20）；C组，Tα1治疗组（移植后给予Tα1 400 μg/kg,n=20）；D组，联合治疗组（移植后给予CsA 10 mg/kg+Tα1 400 μg/kg，n=20）。上述药物每日腹腔注射1次，共注射21 d。观察、记录移植皮片存活情况；各组分别于移植术后第1、7、14、21 d处死5只小鼠，取血行液相芯片细胞因子检测；取移植皮片作HE染色;取小鼠脾脏淋巴细胞行流式细胞术检测T细胞分化。结果 在移植后第1、7、14、21 d，同时点B、C、D组与A组相比，D组分别与B组、C组相比,白细胞介素（IL）-1、IL-2、IL-6、IL-17均降低（ P<0.05），而IL-10均升高（ P<0.05）；而 B、 C两组相比差异无统计学意义。CsA与Tα1单药对细胞因子的作用类似，而联合用药能加强单药效果。B组及D组CD4/CD8比例倒置。D组CD4⁺CD25⁺ T细胞数高于其他组，差异有统计学意义（ P<0.05）。结论 移植后使用Tα1，在一定程度上能减轻T细胞对移植物的损伤，但不能完全阻止排斥反应的发生。

英文摘要:

      Objective To explore the possible mechanism of berberine improve insulin resistance in skeletal muscle of obese rats. Methods Forty Wistar rats were divided into normal control group (NC group, n=10) and high fat food group (HF group, n=30). After the obese model rats established successfully, the rats of NC group (n=10) and HF group (n=10) were sacrificed. The level of fasting plasma endotoxin (ET) was detected. The expression of Toll-like receptor 4 (TLR4) mRNA in skeletal muscle were detected by real time quantitative PCR. The expression of TLR4, IκB kinase β (IKKβ), phospho-IKKβ^Ser181 (p-IKKβ^Ser181), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phospho-IRS-1^Ser307 (p-IRS-1^Ser307) and the tyrosine phosphorylation of IR and IRS-1 (p-IR^Tyr and p-IRS-1^Tyr) protein in skeletal muscle were detected by Western blot. The twenty HF group rats were randomly divided into two group: the fat model control group (FC group, n=10) were fed with high fat diet and distilled water. The fat berberine group (FB group, n=10) were fed with high fat diet and berberine. All rats were sacrificed after effective interventions of eight weeks. The same indexes as the first part of experiment were detected. Results The results showed that the level of ET was increased. The TLR4/IKKβ/NF-κB signaling pathway is activated and the expression of TNF-α was increased of the skeletal muscle in obese rats. However, the insulin signaling pathways of the skeletal muscle in obese rats was inhibited. Berberine could reduce the level of ET of obese rats, down-regulate the TLR4/IKKβ/NF-κB inflammation signaling pathway and improve insulin resistance of skeletal muscle in obese rats. Conclusion Our study revealed that berberine could reduce the level of ET of obese rats, down-regulate the TLR4/IKKβ/NF-κB inflammation signaling pathway in skeletal muscle and berberine can improve insulin resistance of skeletal muscle through inhibiting the active of the TLR4/IKKβ/NF-κB signaling pathway.