| Annexin is a kind of family proteins all of which bind phospholipids in a calcium dependent-manner.160 kinds of unique annexins are identified in more than 65 species from fungi to higher vertebrates. Annexin 5 is the most abundant member of annexin family, accounting for 1% of total cellular protein. Studies show that annexin 5 is identified as a mediator of the anti-inflammatory activity of glucocorticoids via inhibition of phospholipase A2 and an inhibitor of blood coagulation. It also shows protein kinase C inhibitory activity and forms calcium channels on phospholipid membranes. Annexin 5 is widely distributed in many kinds of tissues, such as the thyroid gland, adrenal gland, testis and other endocrine organs in rat, and its distribution shows cell-specific.Stress is a comprehensive response to drastic changes from internal and external environment including mentation, neurology, endocrine, immune and other aspects. The reproductive system is not only an important system involved in stress response, but also susceptible to stress damage. Stress has been a common and important reason of reproductive endocrine disorders. Pathological nerve pain caused by the nerve injury is a kind of constant pain. It shows allodynia and hyperalgesia, and activates the hypothalamus-pituitary-adrenal (HPA) axis and central autonomic system. Many researches indicated that chronic physical and psychological stress could inhibit the function of gonadal axis in male animals, affect sperm production, or even cause permanent infertility. Strong physical and mental stress, chronic stress especially, affects the health of mankind seriously, leading to clinical disease, sub-health status and premature aging. People realize that the development of chronic fatigue syndrome and depression is associated with long-term stress. Stress is harful for reproductive endocrine function and this has been widely recognized by foreign researchers.Our previous studies have found that chronic pain stress could cause significant decrease of annexin 5 expression in mRNA and protein level in the rat testis, reduction of reproduction relative parameters, and inhibite the testosterone secretion; vitro experiments found that annexin 5 can increase the secretion of testosterone in Leydig cells in a dose and time dependent manner. Further experiments confirmed that ERK1/2 MAPK was the key signaling pathways regulating the testosterone synthesis. All of obove suggested annexin 5 may be an important regulatory factor in reproductive endocrine system. the expression of P450scc and 3β-HSD in mRNA and protein level in annexin 5 treated group improved apparently (P<0.01), while there was no change in the expression of StAR mRNA and protein. And the expression of StAR, P450scc and 3P-HSD in sham control group had no difference comparison with those in normal control group. Further more, we used TUNEL assay to detect spermatogenic cell apoptosis and Bax, Bcl-2 and Caspase-3 mRNA expression. The results found that comparing with normal controls, AI,Bax expression and Caspase-3 expression in model control group are all increased obviouly(P<0.01), but Bcl-2 expression decreased (P<0.01). Comparing with the model control group, the mRNA expression of Bax and Caspase-3 are reduced significantly (P<0.01) and Bcl-2 expression raised (P<0.01) in experiment group. Although AI decreased apparently after treated with annexin 5 (P<0.01), there is evident disparity between experiment group and normal controls (P<0.05)Conclusions:The recombinant rat annexin 5 can increase testosterone secretion in rats in a dose-dependent manner. Chronic pain stress induced by spared nerve injury can cause the decrease of the reproduction relative parameters and the level of testosterone. The mechanism of Annexin 5 playing a protective effect on stressed rats, one is elevating the expression of P450scc and 3β-HSD, another is regulating the mRNA expression of Bcl-2 and Caspase-3 to reduce the number of spermatogenic cell apoptosis. |
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