Objective To observe the effects of different energy of extracorporeal shock waves (ECSWs) on diabetic neuralgia in rats.Methods Fifty clean-grade healthy male Sprague-Dawley rats of both sexes,aged 8 weeks,weighing 180-200 g,were divided into 5 groups (n=10 each) using a random number table method:control group (group C),diabetic neuralgia group (group DN),low-energy ECSW group (group L + DN),medium-energy ECSW group (group M + DN),and high-energy ECSW group (group H+DN).Diabetic neuralgia models were established by intraperitoneally injecting streptozotocin (60 mg/kg) in DN,L+DN,M+DN and H+DN groups.ECSWs at 1,2 and 3 bar were applied during 4 consecutive weeks after successful establishment of the model once a week (T1-T4) in L+DN,M+DN and H+ DN groups,respectively.The mechanical paw withdrawal threshold (MWT),thermal paw withdrawal latency (TWL) and motor nerve conduction velocity (MNCV) were measured at T1-T4.Animals were sacrificed after the last measurement,and the sciatic nerve samples were obtained for determination of the expression of tumor necrosis factor-alpha (TNF-α) and interluekin-6 (IL-6) (by Western blot) and expression of TNF-α and IL-6 mRNA (by real-time polymerase chain reaction).Results Compared with group C,MWT,TWL and MNCV were significantly decreased at T1-T4,and the expression of TNF-α and IL-6 protein and mRNA was up-regulated in the other groups (P＜0.05).Compared with group DN,MWT at T2-4 and TWL and MNCV at T3,4 were significantly increased,and the expression of TNF-α and IL-6 protein and mRNA was down-regulated in L+DN,M+DN and H+DN groups (P＜0.05).Compared with group H+ DN,MWT at T2-4 and TWL and MNCV at T3,4 were significantly increased,and the expression of TNF-α and IL-6 protein and mRNA was down-regulated in L+DN and M+DN groups,and the expression of IL-6 mRNA was significantly down-regulated in group L+DN (P＜0.05).Conclusion ECSWs can mitigate diabetic neuralgia in rats,and the low-and medium-energy ECSWs produce better efficacy,and the mechanism is related to inhibiting inflammatory responses.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.