Mechanism of effects of electroacupuncture on memory and cognitive impairment in offspring rats with perinatal nicotine exposure. / ç”µé’ˆå¯¹å›´äº§æœŸå°¼å¤ä¸æš´éœ²å­ä»£å¤§é¼ è®°å¿†å’Œè®¤çŸ¥æŸä¼¤å½±å“çš„æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To observe the effects of electroacupuncture(EA) on memory, cognitive impairment, and the brain-derived neurotrophic factor(BDNF)/N-methyl-D-aspartate receptor subtype 1(NMDAR1) pathway in the brains of offspring rat with intrauterine growth restriction(IUGR) induced by perinatal nicotine exposure(PNE), so as to explore the underlying mechanism. METHODS: SD rats were randomly divided into normal, model, and EA groups, with 4 mothers and 10 offspring rats of each mother in each group. The IUGR model was established by subcutaneous injection of nicotine during pregnancy and lactation. From the 6th day of pregnancy in the mothers until the 21st day after birth of the offspring rats, EA (2 Hz/15 Hz, 1 mA) was administered bilaterally at the "Zusanli"(ST36) of mothers, once daily for 20 min. The brain organ coefficient was used to evaluate the brain development of the offspring rats. The Y-maze test and novel object recognition experiments were performed to assess memory and cognitive function. HE staining was used to observe the development and cellular morphology of the hippocampus and prefrontal cortex in the offspring rats. UV spectrophotometry was used to measure the glutamate(Glu) content in the hippocampus. ELISA was used to detect the BDNF content in the hippocampus. Western blot was performed to measure the protein expression of NMDAR1 in the hippocampus. Immunohistochemistry was used to count the number of BDNF-positive cells in the hippocampus and prefrontal cortex. RESULTS: Compared with the normal group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, contents of BDNF and expression of NMDAR1 proteins in the hippocampus, the number of BDNF-positive cells in the CA1 and CA3 regions of the hippocampus and prefrontal cortex were significantly reduced(P<0.01), while the Glu content in the hippocampus was significantly increased(P<0.01) in the model group of offspring rats；decreased cell number, scattered arrangement, and disrupted cellular structure were observed in the hippocampus and prefrontal cortex of offspring rats in the model group. Compared with the model group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, the BDNF contents and NMDAR1 protein expression in the hippocampus, the number of BDNF-positive cells in the hippocampal CA1 and CA3 regions and prefrontal cortex significantly increased(P<0.01, P<0.05), while the Glu content in the hippocampus was significantly decreased (P<0.01) in offspring rats of the EA group；increased cell number, neat arrangement, and reduced cellular damage were observed in the hippocampus and prefrontal cortex in the EA group. CONCLUSIONS: EA has an improving effect on memory and cognitive function impairment in offspring rats with IUGR induced by PNE, and this mechanism may be associated with the regulation of BDNF/NMDAR1 pathway, thereby improving the neuronal quantity and structure of the hippocampus and prefrontal cortex in offspring rats.

Comparison of Protective Effects of Electroacupuncture at ST 36 and LU 5 on Pulmonary and Hypothalamic Pituitary Adrenal Axis Changes in Perinatal Nicotine-Exposed Rats.

BACKGROUND: Maternal smoking and/or exposure to environmental tobacco smoke continue to be significant factors in fetal and childhood morbidity and are a serious public health issue worldwide. Nicotine passes through the placenta easily with minimal biotransformation, entering fetal circulation, where it results in many harmful effects on the developing offspring, especially on the developing respiratory system. OBJECTIVES: Recently, in a rat model, electroacupuncture (EA) at maternal acupoints ST 36 has been shown to block perinatal nicotine-induced pulmonary damage; however, the underlying mechanism and the specificity of ST 36 acupoints for this effect are unknown. Here, we tested the hypothesis that compared with EA at ST 36, EA at LU 5 acupoints, which are on lung-specific meridian, will be equally or more effective in preventing perinatal nicotine-induced pulmonary changes. METHODS: Twenty-four pregnant rat dams were randomly divided into 4 groups: saline ("S"), nicotine ("N"), nicotine + ST 36 (N + ST 36), and nicotine + LU 5 (N + LU 5) groups. Nicotine (1 mg/kg, subcutaneously) and EA (at ST 36 or LU 5 acupoints, bilaterally) were administered from embryonic day 6 to postnatal day 21 once daily. The "S" group was injected saline. As needed, using ELISA, western analysis, q-RT-PCR, lung histopathology, maternal and offspring hypothalamic pituitary adrenal axes, offspring key lung developmental markers, and lung morphometry were determined. RESULTS: With nicotine exposure, alveolar count decreased, but mean linear intercept and septal thickness increased. It also led to a decrease in pulmonary function and PPARγ and an increase of ß-catenin and glucocorticoid receptor expression in lung tissue and corticosterone in the serum of offspring rats. Electroacupuncture at ST 36 normalized all of these changes, whereas EA at LU 5 had no obvious effect. CONCLUSION: Electroacupuncture applied to ST 36 acupoints provided effective protection against perinatal nicotine-induced lung changes, whereas EA applied at LU 5 acupoints was ineffective, suggesting mechanistic specificity and HPA axis' involvement in mediating EA at ST 36 acupoints' effects in mitigating perinatal nicotine-induced pulmonary phenotype. This opens the possibility that other acupoints, besides ST 36, can have similar or even more robust beneficial effects on the developing lung against the harmful effect of perinatal nicotine exposure. The approach proposed by us is simple, cheap, quick, easy to administer, and is devoid of any significant side effects.

[Electroacupuncture at "Zusanli" (ST36) and "Chize" (LU5) of mother rats exposed to nicotine during pregnancy and lactation has a protective effect on development of lung function and morphology in neonatal rats].

OBJECTIVE: To compare the different effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Chize" (LU5) of mother rats exposed to Nicotine during pregnancy and lactation on lung function and morphological changes in offspring rats, so as to explore the most effective acupoint for improving the development of lung in neonatal rats. METHODS: A total of 24 female pregnancy SD rats were randomly divided into 4 groups: normal control, model, EA-ST36 and EA-LU5 (n＝6 rats in each group). Rats of the normal group were treated by subcutaneous injection of normal saline, and those of the other 3 groups treated by subcutaneous injection of nicotine (1 mg•kg－1•d－1) beginning from the 6th day to about the 21st day of pregnancy (childbirth day) for nicotine exposure during pregnancy and lactation. The daily EA treatment (2 Hz /15 Hz，1 mA) was applied to bilateral ST36 and LU5 for 20 min, beginning from the 6th day of pregnancy to the 21st day (childbirth day). The lung function of the offspring rats including the peak inspiratory flow (PIF), peak expiratory flow (PEF), lung resistance (RL), exhalation resistance (RE)and lung dynamic compliance (Cdyn) was detected by using a lung function analysis system. Histopathological changes (severity of alveolarization) of the offspring rats' lung tissue were observed under microscope after H．E. stain. RESULTS: Compared with the normal group, the PIF, RL and RE values were significantly increased (P<0.01), and PEF and Cdyn values significantly decreased in the model group (P<0.01). The alveolar diameter in the model group was evidently increased relevant to the normal group (P<0.01). Following the intervention, modeling induced increase of PIF, RL, RE and alveolar diameter and decrease of PEF and Cdyn values in the EA-ST36 group, and the increased PIF, RL and RE levels in the EA-LU5 group were obviously suppressed relevant to the model group (P<0.01, P<0.05). Additionally, modeling induced obvious congestion and edema of the alveolar wall, alveolar deformation, rupture and fusion, and reduction of the number of the pulmonary alveoli were evidently milder in both EA-ST36 and EA-LU5 groups. No significant differences were found between the EA-ST36 and EA-LU5 groups in the abovementioned 5 indexes of pulmonary function and alveolar diameter (P>0.05)．. CONCLUSION: EA of ST36 and LU5 of mother rats experiencing nicotine exposure during pregnancy and lactation can improve the lung function and morphological changes in neonatal rats, and the effect of ST36 is relatively better.

A cell-molecular approach predicts vertebrate evolution.

In contrast to the conventional use of genes to determine the evolution of phenotypes, we have functionally integrated epithelial-mesenchymal interactions that have facilitated lung phylogeny and ontogeny in response to major geologic epochs. As such, this model reveals the underlying principles of lung physiology based on the evolutionary interactions between internal and external selection pressures, providing a novel understanding of lung biology. As a result, it predicts how cell-molecular changes in this process can cause disease and offers counterintuitive insights to diagnosis and treatment based on evolutionary principles.