Objective To analyze the effect of ginger root extract (GRE) on learning and memory function and nerve cell structure in rats exposed to aluminum, and to explore its possible mechanism based on calmodulin⁃dependent protein kinase Ⅱ (CaMKⅡ), neuronal nitric oxide synthase (nNOS) and protein kinase C (PKC). Methods  A total of 36 SD male rats were randomly assigned to blank control group, aluminum exposed group, clinical drug group, low⁃dose GRE group (L⁃GRE group), medium⁃dose GRE group (M⁃GRE group) or high⁃dose GRE group (H⁃GRE group), with 6 rats in each group. Rats in the blank control group freely drank water without aluminium chloride, and rats in the remaining groups drank water containing 10 mg/mL crystallization of aluminium chloride. After 3 months, intragastric administration of normal saline was given to the blank control group and the aluminum exposed group, whereas intragastric administration of donepezil hydrochloride solution was given to the clinical drug group; in addition, intragastric administration of 100 mg/kg, 200 mg/kg, and 400 mg/kg GRE solutions was given to the L⁃GRE, M⁃GRE, and H⁃GRE groups, respectively. After 4 weeks of continuous intervention, Morris water maze test was used to evaluate learning and memory function of rats. The morphological changes of hippocampus tissues in rats were observed by the HE staining. The mRNA and protein expressions of CaMKⅡ, nNOS, and PKC in hippocampus tissues of rats were detected by employing the real⁃time fluorescent quantitative PCR and Western blot, respectively. Results (1) Compared with the blank control group, rats of the aluminum exposed group exhibited a prolong period of escape latency, and decreased frequency of platform crossing (P<0.05), as well as presented as shriveled nerve cells in hippocampus tissues, and significantly reduced number of nerve cells; in addition, the aluminum exposed group yielded decreased mRNA expressions of CaMKⅡ, nNOS, and PKC, and decreased protein expressions of nNOS and PKC (P<0.05). (2) Compared with the aluminum exposed group, the L⁃GRE, M⁃GRE, and H⁃GRE groups exhibited a shortened period of escape latency, and the clinical drug group, M⁃GRE and H⁃GRE groups yielded increased frequency of platform crossing (P<0.05); furthermore, hippocampus tissues of rats in various administration groups presented as ameliorated pathomorphism in varying degrees; in addition, the mRNA expressions of CaMKⅡ, nNOS, and PKC were elevated in the clinical drug group, and the mRNA and protein expressions of nNOS and PKC were elevated in various⁃dose GRE groups (P<0.05). (3) Compared with the clinical drug group, there was no statistically significant difference in escape latency period of rats between the M⁃GRE group and the H⁃GRE group, as well as the frequency of platform crossing and the residence time of the target quadrant between various⁃dose GRE groups (P>0.05), and hippocampus tissues of rats in various⁃dose GRE groups presented as more significant improvement of pathomorphism; moreover, the expressions of nNOS and PKC proteins were elevated in the M⁃GRE group and the H⁃GRE group, and the L⁃GRE group interpreted an elevated protein expression of nNOS (P<0.05). (4) There was no statistically significant difference in escape latency period, the frequency of platform crossing and residence time of the target quadrant between various⁃dose GRE groups (P>0.05). With the increase of GRE intervention dose, the improvement effect of pathomorphism in hippocampus tissues of rats was more obvious. CaMKⅡ mRNA expression in the H⁃GRE group was higher than that in the L⁃GRE group (P<0.05). Conclusion GRE can ameliorate the structure of nerve cells and learning and memory function in rats exposed to aluminum, therein its improvement effect on nerve cell structure is superior to donepezil hydrochloride, and its improvement effect on learning function is comparable to donepezil hydrochloride. GRE's mechanism may be related to the decreased expressions of CaMKⅡ, nNOS, and PKC induced by antagonistic aluminum.

无