| [Object]To observe the effect and mechanism of Tang Bi Kang(TBK) treating diabetic rats peripheral neuropathy by regulating the sciatic nerve NF-KB/Nrf2 signal pathway.[Methods]85 Male SD rats were used. All the rats were adaptively fed for one week.10 of these were randomly assigned to the normal group based on body weight. The others were used as diabetic rats models induced by high-fat diet for 4 weeks combined with low dose of streptozotocin (STZ,35mg/kg) injection. After that, the diabetic rats with level of random blood glucose higher than 16.7mmol/L and stable for 72h were randomly divided into model group, alpha lipoic acid (ALA)group, high dose, medium dose and low dose of TBK groups with 10 rats in each group. The treatment lasted for 12 weeks. The general condition, body weight and blood glucose of rats were recorded in the experiment. After 12 weeks of treatment, the sciatic nerve conduction velocity was measured and the rats were sacrificed. The morphological changes were observed by HE and Weil’s staining. The concentration of IL-6, TNF-α, GSH-px, SOD and MDA in serum were detected. The target protein like NF-κB, Keap1, Nrf2, GCLc, IκBα and GST pi were detected by western blot. The mRNA expressions of NF-κB, Keap1, Nrf2, GCLc, IκBα and GST pi were detected by Real-time PCR.[Results]After treatment for 12 weeks, body weight of rats in model group was significantly decreased (p<0.01 or p<0.05). Compared with the model group, body weight of TBK high dose group significantly increased (p<0.05). After 12 weeks, blood glucose of rats in model group was significantly increased (p<0.05 or p<0.01). Compared with the model group, random blood glucose of rats in ALA group, TBK high dose group was significantly decreased (p<0.01 or p<0.05). HE and Weil’s staining showed that the morphological changes of sciatic nerve morphology in all treatment groups were smaller than that in model group. After 12 weeks, inflammation and oxidative stress related indices in serum showed that compared with normal group, IL-6 and TNF-a were significantly increased in the model group (p<0.01).Compared with model group, IL-6 content decreased significantly in each treatment group (p<0.05 or p<0.01) while the content of TNF-a was significantly decreased in ALA group and in high dose group (p<0.01). Compared with the normal group, the levels of SOD and GSH-px were significantly lower in diabetic groups (p<0.01). Compared with the model group, the levels of SOD and GSH-px were significantly increased(p<0.01) in treatment groups. Compared with normal group, MDA content was significantly increased inthe model group (p<0.01), while ALA group, medium and low dose TBK groups were decreased significantly compared with the model group (p<0.05 or p<0.01). Compared with the normal group, the expressions of NF-κB, IκBα and Keapl protein as well as NF-κB and Keapl mRNA were significantly increased in the model group. Compared with the model group, ALA and TBK groups showed different degrees of down regulated the expressions of NF-κB, IκBα and Keapl protein as well as NF-κB and Keapl mRNA. Meanwhile, compared with the normal group, the expressions of Nrf2, GCLc, GST Pi protein and mRNA were significantly decreased in the model group. Compared with the model group, ALA and TBK groups showed different degrees of up regulated expressions of Nrf2, GCLc, GST Pi.[Conclusions]After treated by TBK, the conduction velocity of sciatic nerve in diabetic rats was significantly increased and the pathological changes were reduced that indicated TBK could effectively improved sciatic nerve function and morphology so as to protect and repair the injury of sciatic nerve in diabetic rats.Possible mechanism:TBK can inhibit NF-κB signaling pathway and reduce the downstream IL-6 and TNF-α production to decrease the inflammatory damage, meanwhile it regulated Keapl-Nrf2 signaling pathway which increased the production antioxidant enzyme SOD and GSH-px. TBK could increase the antioxidant ability, and reduce phase II enzymes-GCLc and GST Pi activating Keapl-Nrf2 signaling pathway so as to protect and repair the injury of sciatic nerve in diabetic rats.
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