硫酸镁不同用药时限对子痫前期大鼠模型母胎影响的研究

发布时间：2018-05-13 04:36

本文选题：子痫前期 + 动物模型　；参考：《广西医科大学》2014年硕士论文

【摘要】：目的：观察研究硫酸镁不同用药时限治疗对子痫前期大鼠模型孕鼠及胎鼠的影响，及对胎脑海马中微管相关蛋白2（MAP-2）mRNA、半胱氨酸天冬氨酸蛋白酶3（caspase-3）mRNA表达的影响，及其作用机制。方法：将确定妊娠的SD大鼠随机分为正常妊娠对照组、子痫前期模型组、硫酸镁治疗1天组、2天组、4天组，每组6只。于妊娠第14天，除正常妊娠对照组外其余4组孕鼠予低剂量内毒素（1.0g/kg）诱导建立子痫前期大鼠模型。治疗组分别予硫酸镁1天、2天、4天不同用药时限治疗，观察其对孕鼠血压、尿蛋白的影响。于妊娠第20天剖宫取胎，测量新生鼠身长、体重。再取胎盘组织、胎鼠脑组织固定，观察各组胎盘HE染色下组织形态学改变，TUNEL法检测各组胎脑海马CA1区神经细胞凋亡情况，通过荧光定量PCR（RT-pPCR）测定各组胎脑海马中MPA-2mRNA及caspase-3mRNA的表达情况。结果：（1）妊娠第15天，除正常妊娠对照组外其余4组孕鼠收缩压均较自身基础压升高30mmHg，差异有统计学意义（P0.05），子痫前期模型组血压升高并持续至分娩。予硫酸镁用药后，孕期硫酸镁各治疗组大鼠血压较妊娠第15天明显降低。妊娠第19天，硫酸镁用药2天组、4天组大鼠血压较模型组明显降低，差异有统计学意义（P0.05），两组间比较差异无统计学意义（P0.05）。正常妊娠对照组孕期血压无明显变化。（2）妊娠第15天，除正常妊娠对照组外其余4组孕鼠24h尿蛋白水平均高于基础值2倍以上，与正常妊娠对照组比较，差异有统计学意义（P0.05）。（3）各组胎鼠身长、体重等生长发育指标比较，差异均无统计学意义（P0.05）。（4）胎盘组织病理学可见子痫前期模型组呈现基带炎性细胞浸润、迷路带组织核碎裂、纤维蛋白沉积等胎盘炎性改变，硫酸镁各治疗组上述病变明显较轻，各治疗组间差异不明显。（5）TUNLE检测显示硫酸镁治疗1天组、2天组、4天组胎脑海马CA1区神经细胞凋亡数明显低于模型组，差异有统计学意义（P0.05）。硫酸镁治疗2天组、4天组较治疗1天组明显改善，，差异有统计学意义（P0.05）。但治疗2天组、4天组之间比较无统计学意义（P0.05）。（6）与正常妊娠对照组比较，子痫前期模型组、硫酸镁治疗1天组、2天组、4天组的新生大鼠海马组织中MAP-2mRNA表达量均降低，差异有统计学意义(P0.05)。硫酸镁各治疗组MAP-2mRNA的表达量较模型组高，差异有统计学意义（P0.01）。硫酸镁治疗2天组、4天组MAP-2mRNA的表达量较硫酸镁治疗1天组高，差异有统计学意义（P0.05）。但硫酸镁治疗2天组、4天组之间比较差异无统计学意义（P0.05）。(7)与正常妊娠对照组比较，子痫前期模型组、硫酸镁治疗1天组、2天组、4天组的新生大鼠海马组织中caspase-3mRNA表达量均升高，差异有统计学意义(P0.05)。硫酸镁各治疗组caspase-3mRNA的表达量较模型组低，差异有统计学意义（P0.01）。硫酸镁治疗2天组、4天组caspase-3mRNA的表达量较硫酸镁治疗1天组低，差异有统计学意义（P0.05）。但硫酸镁治疗2天组、4天组之间比较差异无统计学意义（P0.05）结论：（1）低剂量内毒素能成功建立子痫前期大鼠模型，产生高血压、蛋白尿、胎盘病理学等相应表现。（2）硫酸镁对子痫前期模型孕鼠有一定的疗效，表现出间接的降压作用，并对胎盘功能有一定的改善，无明显毒副反应。（3）硫酸镁对子痫前期胎脑有一定的治疗作用，其保护机制可能与上调对胎脑MAP2mRNA表达及下调对caspase-3mRNA表达有关。（4）硫酸镁用药2天组对子痫前期母胎的疗效较硫酸镁用药1天组、4天组好。
[Abstract]:Objective: To observe and study the effects of different medication time of Magnesium Sulfate on pregnant rats and fetal rats in preeclampsia model, and the effect on the expression of microtubule related protein 2 (MAP-2) mRNA and cysteine aspartic proteinase 3 (caspase-3) mRNA in the hippocampus of fetal brain and its mechanism.
Methods: the SD rats were randomly divided into normal pregnancy control group, preeclampsia model group, Magnesium Sulfate treatment group for 1 days, 2 days group, 4 day group, 6 rats in each group. The other 4 groups of pregnant rats were given low dose endotoxin (1.0g/kg) to establish the preeclampsia rat model except the normal pregnancy control group. The treatment group was given Magnesium Sulfate 1, respectively. 2 days, 2 days, 4 days of different medication time treatment, observe the effect on the blood pressure and urine protein of pregnant rats. On the twentieth day of pregnancy, the body length and body weight of the newborn rats were measured. The placenta tissue and the fetal rat brain were fixed. The histomorphological changes of the placenta in each group were observed by HE staining. The apoptosis of the hippocampal CA1 area of the fetal brain was detected by TUNEL method. The expression of MPA-2mRNA and caspase-3mRNA in the hippocampus of fetal brain of each group was detected by fluorescent quantitative PCR (RT-pPCR).
Results: (1) on the fifteenth day of pregnancy, the systolic pressure of the other 4 groups of pregnant rats except the normal pregnancy control group increased by 30mmHg. The difference was statistically significant (P0.05). The blood pressure of the preeclampsia model group increased and continued to labor. After Magnesium Sulfate, the blood pressure of the rats in each group of pregnant Magnesium Sulfate was significantly lower than that of the pregnancy. The pregnancy rate was nineteenth. The pregnancy rate was nineteenth. In the 2 day group of Magnesium Sulfate, the blood pressure of the 4 day group was significantly lower than that of the model group (P0.05). There was no significant difference between the two groups (P0.05). (2) the fifteenth days of pregnancy, the other 4 groups of pregnant rats except the normal pregnancy control group were higher than the basic value 2. Compared with the normal pregnancy control group, the difference was statistically significant (P0.05). (3) there was no significant difference in the growth and development indexes of fetal rats, such as body length and weight (P0.05). (4) placental histopathology showed that the model group of preeclampsia presented basic inflammatory cell infiltration, labyrinthine tissue fragmentation, fibrin deposition and other placenta The pathological changes in the Magnesium Sulfate treatment group were lighter, and the difference between the treatment groups was not obvious. (5) TUNLE detection showed that the number of neuronal apoptosis in the CA1 region of the fetal brain hippocampus was significantly lower than that of the model group in the 1 day group, the 2 day group and the 4 day group, the difference was statistically significant (P0.05). The 4 day group was significantly improved than the 1 day group. The difference was statistically significant (P0.05), but there was no significant difference between the 2 days group and the 4 day group (P0.05). (6) compared with the normal pregnancy control group, the preeclampsia model group, the 1 day Magnesium Sulfate treatment group, the 2 day group, the 4 day group of newborn rats were all decreased in the hippocampus, the difference was statistically significant (P0.05). Each treatment was statistically significant (P0.05). The expression of MAP-2mRNA was higher than that of the model group (P0.01). The expression of MAP-2mRNA in the 2 day group was higher than that in the 4 day group, and the difference was statistically significant (P0.05). However, there was no significant difference between the 2 days group of Magnesium Sulfate treatment and the 4 day group (P0.05). (7) compared with the normal pregnancy control group, the difference was not statistically significant (P0.05). In the preeclampsia model group, the expression of caspase-3mRNA in the hippocampus of the 1 day group, the 2 day group and the 4 day group was increased, and the difference was statistically significant (P0.05). The expression of caspase-3mRNA in each group of Magnesium Sulfate was lower than that of the model group (P0.01). The expression of caspase-3mRNA in the 4 day group of Magnesium Sulfate treatment and the expression of caspase-3mRNA in the 4 day group were expressed. The difference was statistically significant (P0.05), but there was no significant difference between the 2 day group and the 4 day group (P0.05). The difference between the 1 groups was statistically significant (P0.05).
Conclusions: (1) low dose endotoxin can successfully establish preeclampsia rat model and produce hypertension, proteinuria and placental pathology. (2) Magnesium Sulfate has a certain effect on the preeclampsia model pregnant rats, showing indirect antihypertensive effect, and having some improvement on placental function and no obvious side effects. (3) Magnesium Sulfate before epilepsy. The protective mechanism of fetal brain may be related to the up regulation of MAP2mRNA expression and down regulation of caspase-3mRNA in fetal brain. (4) the effect of the 2 day Magnesium Sulfate drug group on the preeclampsia mother fetus is better than that of the 1 day group of Magnesium Sulfate.

【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R714.244

【参考文献】