| Part I Ultrapathological examination of copper/low-density polyethylene nanocomposite on the endometrium in ratsObjective: To evaluate the safety of copper/low-density polyethylene nanocomposite by ultrastructural observation on the endometrium in rats.Methods: Mature female Sprague-Dawley (SD) rats were randomly divided into 5 groups: bulk copper group (Cu group), LDPE group, copper/low-density polyethylene nanocomposite (nano-Cu/ LDPE) groups I and II (copper ion released at 5~10 and 10~20μg/220 mm2/day, respectively), sham-operated control group (SO group). Each corresponding material was inserted into the unilateral uterine horn. Then the endometria of the material-bearing uterine horns were collected and observed by transmission electron microscope technique at the 30th day after insertion.Result: Under the electron microscope, obvious morphologic changes of the endometria of the rats in the Cu group were observed, such as the decreased density of microvilli on the surfaces of endometrial cells, the elongated mitochondria in the epithelial cells with obviously dilated cell plasma membranes, numerous preformed lysosomes in glandular epithelial cells. Whereas, no remarkable morphologic changes were observed in the nano-Cu/ LDPE groups.Conclusion: Compared with conventional bulk copper material, the nano-Cu/ LDPE has less effect on the ultrastructure of endometrium and induces minor endometrium damage. It may be one mechanism of this material on relieving the side-effect of copper bearing IUD insertion.Part II The effect of copper/low-density polyethylene nanocomposite on the levels of some corresponding factors in endometrium of ratsTo explore the possible mechanism of copper/low-density polyethylene nanocomposite on relieving the side-effects of IUD insertion, the endometrial levels of some factors which related to bleeding and pain after the material insertion were observed. This part included two experiments:Experiment One Determination of the tPA and PGE2 levels in the endometrial tissue homogenate after copper/low-density polyethylene nanocomposite insertion in rats.Objective: To study the influence of nano-Cu/ LDPE on the tPA and PGE2 levels in endometrium and to explore the possible mechanism of the influence of this material on the side-effect of IUD insertion.Methods:. Grouping and material inserting were the same as part I. The endometrial tissue homogenates were collected and the tPA and PGE2 levels were determined by using of ELISA at 30th and 60th day after material insertion, respectively.Result: Compared with those in SO group, the concentrations of PGE2 and tPA in all experimental groups except for PGE2 levels in LDPE group were obviously increased at Day 30 after insertion, and these parameters in nano-Cu/ LDPE groups were significantly lower with comparison to those in Cu group (P<0.05). At Day 60 after insertion, tPA levels were still higher in Cu group and nano-Cu/ LDPE groups, but there was no difference of PGE2 levels in all groups except for Cu group. For the same experimental group, no obvious change occurred for tPA levels and all PGE2 levels have decreased except for LDPE group from 30th to 60th day after insertion.Conclusion: Compared with traditional bulk copper material, the nano-Cu/ LDPE has less influence on the endometrial PGE2 and tPA levels. This may be one of the mechanism of this material on relieving the side-effect of IUD insertion.Experiment Two The effect of copper/low-density polyethylene nanocomposite on the expression of PAI-1,SP,SP-R proteins of the endometrium in rats.Objective: To study the effect of copper/low-density polyethylene nanocomposite on the expression of PAI-1, SP, SP-R proteins of the endometrium in rats and to explore the possible mechanism of the influence of this material on the side-effect of IUD insertion.Methods: Grouping and material inserting were the same as part I. The endometrial tissues were collected and imbeded by paraffin at 90th and 180th day after material insertion, respectively. Then the expression of PAI-1,SP and SP-R proteins were observed by method of the immunohistochemistry.Result: The PAI-1 protein expressed mainly on endochylema of vessel endothelial cells and epithelioglandular cells. Much obvious expression was observed in the endometrium of nano-Cu/ LDPE group. As the same, the SP and SP-R proteins also expressed mainly on endochylema of vessel endothelial cells and epithelioglandular cells whereas the much obvious expression was observed in the endometrium of Cu group. The average optical density of positive products within cells were measured and analyzed which showed the following result. At 90th day after insertion, there was no difference for PAI-1 expression in the endometrium between nano-Cu/ LDPE and Cu group, nano-Cu/ LDPE group I and SO group, but a lower expression in the endometrium of nano-Cu/ LDPE group II than that of SO group. No difference for SP expression in the endometrium among nano-Cu/ LDPE groups and SO group but obvious lower expression in the endometrium of nano-Cu/ LDPE group I than that of Cu group. The SP-R expression in the endometrium of nano-Cu/ LDPE groups were higher than that of SO group but lower than that of Cu group. At 180th day after insertion, no difference of PAI-1 expression in the endometrium of nano-Cu/ LDPE groups and Cu group were observed. Compared with that of SO group, the SP expression in the endometrium of nano-Cu/ LDPE groups showed no obvious difference whereas higher expression was detected in the endometrium of Cu group. For nano-Cu/ LDPE groups, SP-R expression was the same with that of Cu group but higher than that of SO group. From 90th to 180th day after insertion, no difference exisited for the PAI-1 and SP expression in the same group but obvious decrease of SP-R experssion for each experimental group was observed.Conclusion: Compared with traditional bulk copper material, the nano-Cu/ LDPE has less influence on the expression of PAI-1, SP, SP-R proteins in endometrum. This may be one of the mechanism of this material on relieving the side-effect of IUD insertion.
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