Low-molecular-weight heparin protects kidney through an anti-apoptotic mechanism in a rat pre-eclamptic model
research target：Low-molecular-weight heparin
Periodicals：European Journal of Obstetrics & Gynecology & Reproductive Biology
IF：1.69
Cooperative Unit：Guangzhou Southern Hospital
Time of publication：February，2015
Summary
Objective：To investigate the effect of low-molecular-weight heparin (LMWH) for the treatment of pre-eclampsia (PE) and the underlying mechanism.
Study design：PE was established in a rat model using l-NG-nitroarginine methyl ester (l-NAME). The effect of LMWH was examined by measuring various physiological parameters known to be associated with PE.
Results：Blood pressure, urinary protein, blood urea nitrogen and serum creatinine were higher in l-NAME-treated rats compared with control rats. In addition, the number of fetuses, and the weight of fetuses and placentas was lower in l-NAME-treated rats, indicating the establishment of PE conditions. Apoptosis was found in kidney tissue in l-NAME-treated rats. LMWH treatment restored the PE-associated disorders, and inhibited apoptosis in kidney tissue in these rats.
Conclusions：LMWH can control PE conditions, protect renal function and improve fetal health. The mechanism of renal protection is likely to be related to the inhibitory effect of LMWH on apoptosis in kidney tissue. This study provides evidence that LMWH can potentially be used as a safe and effective anti-PE drug to improve PE conditions and protect renal function by inhibiting PE-induced apoptosis.
1. Based on the WB test results, the urine protein levels of the non-pregnant samples were similar, and the urine protein level of the blank group was the same as that of the non-pregnant group. In the PE group, the urine protein level was significantly higher than that of the blank group, indicating that PE caused renal dysfunction. In nude mice treated with LMWH, the urinary protein level at 20 days of gestation was reduced to a level similar to that of the blank group, indicating that LMWH treatment can restore renal function.
2. LMWH inhibits apoptosis of renal tissue cells
Taking the number of apoptotic cells per 100 total cells as the apoptotic index, compared with the blank control group, the apoptotic index of the non-pregnant group was lower, and the apoptosis index of the PE group was higher.However, the apoptotic index was reduced after LMWH treatment, and the apoptotic index returned to the level of the blank group.
3. LMWH affects the mRNA levels of caspase-3, Bcl-2 and Bax
To investigate whether PE induces apoptosis in renal tissue cells, the mRNA levels of caspase-3, Bcl-2 and Bax were quantitatively detected by PCR.The results showed that compared with the blank control group and the non-pregnant group, the mRNA levels of caspase-3 and Bax in the PE group were significantly increased, and the mRNA level of Bcl-2 was significantly decreased.It was proved that PE can induce apoptosis of renal tissue cells.Compared with the blank control group, the mRNA levels of caspase-3, Bax and Bcl-2 were recovered after LMWH treatment, but did not reach the blank group level.These results confirm that LMWH treatment can improve PE and inhibit apoptosis of renal tissue cells.
References
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