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2017 ; 130
(9
): 1033-1041
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Effects of Rapamycin on Clinical Manifestations and Blood Lipid Parameters in
Different Preeclampsia-like Mouse Models
#MMPMID28469097
Yi YH
; Yang Z
; Han YW
; Huai J
Chin Med J (Engl)
2017[May]; 130
(9
): 1033-1041
PMID28469097
show ga
BACKGROUND: The pathogenesis of some types of preeclampsia is related to fatty
acid oxidation disorders. Rapamycin can regulate fatty acid metabolism. This
study aimed to investigate the effects of rapamycin on the clinical
manifestations and blood lipid parameters in different preeclampsia-like mouse
models. METHODS: Two preeclampsia-like mouse models and a control group were
established: L-NA (injected with N?-nitro-L-arginine methyl ester), LPS (injected
with lipopolysaccharide), and the control group with normal saline (NS). The
mouse models were established at preimplantation (PI), early- and late-pregnancy
(EP, LP) according to the time of pregnancy. The administration of rapamycin (RA;
L-NA+RA, LPS+RA, and NS+RA) or vehicle as controls (C; L-NA+C, LPS+C, NS+C) were
followed on the 2nd day after the mouse models' establishment. Each subgroup
consisted of eight pregnant mice. The mean arterial pressure (MAP), 24-h urinary
protein, blood lipid, fetus, and placental weight were measured. The
histopathological changes and lipid deposition of the liver and placenta were
observed. Student's t-test was used for comparing two groups. Repeated measures
analysis of variance was used for blood pressure analysis. Qualitative data were
compared by Chi-square test. RESULTS: The MAP and 24-h urinary protein in the PI,
EP, and LP subgroups of the L-NA+C and LPS+C groups were significantly higher
compared with the respective variables in the NS+C group (P < 0.05). The
preeclampsia-like mouse models were established successfully. There was no
significant difference in the MAP between the PI, EP, and LP subgroups of the
L-NA+RA and L-NA+C groups and the LPS+RA and LPS+C groups. The 24-h urine protein
levels in the PI and EP subgroups of the L-NA+RA group were significantly lower
compared with the respective levels in the L-NA+C groups (1037 ± 63 vs. 2127 ±
593 ?g; 976 ± 42 vs. 1238 ± 72 ?g; bothP < 0.05), also this effect appeared
similar in the PI and EP subgroups of the LPS+RA and LPS+C groups (1022 ± 246 vs.
2141 ± 432 ?g; 951 ± 41 vs. 1308 ± 30 ?g; bothP < 0.05). The levels of serum-free
fatty acid (FFA) in the PI and EP subgroups of the L-NA+RA groups were
significantly lower compared with the respective levels in the L-NA+C group (2.49
± 0.44 vs. 3.30 ± 0.18 mEq/L; 2.23 ± 0.29 vs. 2.84 ± 0.14 mEq/L; bothP < 0.05).
The levels of triglycerides (TG) and total cholesterol in the PI subgroup of the
L-NA+RA group were significantly lower compared with the respective levels in the
L-NA+C (1.51 ± 0.16 vs. 2.41 ± 0.37 mmol/L; 2.11 ± 0.17 vs. 2.47 ± 0.26 mmol/L;
bothP < 0.05), whereas high-density lipoprotein serum concentration was
significantly higher (1.22 ± 0.19 vs. 0.87 ± 0.15 mmol/L;P < 0.05) and
low-density lipoprotein serum concentration did not exhibit a significant
difference. There were no significant differences in the FFA of the PI, EP, and
LP subgroups between the LPS+RA and the LPS+C groups. The levels of TG in the PI
subgroup of the LPS+RA group were significantly lower compared with the
respective levels in the LPS+C group (0.97 ± 0.05 vs. 1.22 ± 0.08 mmol/L;P <
0.05). CONCLUSION: Rapamycin can improve clinical manifestations and blood lipid
profile in part of the preeclampsia-like mouse models.