肺臟以及腦內的呼吸控制中樞在早產兒身上尚未完全成熟。若早產兒合併低出生體重，常因呼吸窘迫引發慢性肺部疾病引發多重器官衰竭導致死亡。新生兒加護病房自80年代開始，常使用合成的醣皮質類固醇Dexamethasone(Dex)用以避免早產新生兒因呼吸窘迫。(Taeusch HW. 1975; Mammel MC. et al., 1983; Avery GB.et al.,1985; Cummings JJ. 1989)。Dex的副作用除了造成高血壓、腸穿孔、心室肥大、代謝異常等外，研究指出接受類固醇治療的早產兒會造成大腦灰質及大腦容量的減少，身高較矮、體重較輕、頭圍較小，並出現神經功能的異常。(Yeh TF. et al., 1998;2004)。然而Dex在目前的新生兒急救復甦過程以及訓練移除呼吸器過程仍扮演一個相當重要的角色。
海馬迴是腦內負責學習、記憶形成的重要邊緣系統構造之一。海馬迴中的齒狀迴有神經細胞新生的作用。而針刺是傳統醫學中的一種治療方式，有研究證實針刺足三里可以促進成鼠海馬迴細胞的增生。(Hwang IK. et al., 2010)。足三里是足陽明胃經的第36個腧穴(ST-36)，位於膝下三寸，長總趾伸肌與前脛骨肌間，距脛骨一橫指處。本實驗探討針刺足三里能否改善醣皮質類固醇對早產兒所造成的神經傷害。於出生後一日齡幼鼠腹腔注射單一高劑量的Dex (0.5 mg/kg)，分別於出生後第3天、第7天連續針刺足三里三天以探討海馬迴細胞再生的能力。以5-Bromo-2’-deoxyuridine (BrdU)作為細胞增生的指標。以螢光免疫染色觀察齒狀迴中Neuronal nuclei (NeuN)和Glial fibrillary acidic protein (GFAP)區別增生的前驅細胞是否分化成神經細胞或神經膠細胞。
結果在P3及P7組接受Dexamethasone 腹腔內注射的幼鼠,其增加體重/ P1體重 百分比明顯較生理食鹽水腹腔內注射的幼鼠低。在P3生理食鹽水組和P7針刺組的腦室周圍亦有明顯的BrdU反應的細胞，其大小較一般同時期的神經元稍大。
另外在齒狀迴的BrdU(+) & NeuN(+)雙重螢光染色細胞密度明顯較BrdU(+) & GFAP(+)雙重螢光染色細胞密度高。在normal saline (N/S) control 組的BrdU(+) & NeuN(+)雙重螢光染色細胞集中在齒狀迴顆粒層的外側。而在實驗組則沒觀察到這種現象。經過Image Pro-plus計算齒狀迴的BrdU(+) & NeuN(+)雙重螢光染色細胞密度發現Dex組較N/S組低，acupuncture 組較Dex高但仍略低於N/S組。
結論是齒狀迴新生的細胞以神經細胞為多，而針刺治療可以改善Dex造成海馬迴神經細胞的傷害，促進神經細胞的增生。

Dexamethasone (a synthetic glucocorticoid) is widely used to treat adults’ inflammatory and autoimmune diseases. In preterm infants’ long term follow up, dexamethasone has central nervous side effects, such as neurologic dysfunction, decreasing brain volume and learning potential. However, dexamethasone is still used in preterm infants’ neonatal respiratory distress syndrome while surfactant and emergent resuscitation are useless.
The hippocampus is rich in glucocorticoid receptors and belongs to the limbic system. The hippocampus plays important roles in long-term memory, spatial navigation, and related to mental illness. This study attempted to find out the hippocampus status after dexamethasone treatment.
Wistar neonatal rats were for animal model. Two major groups are determinated P3 (post natal day 3) and P7 (post natal day 7). In P3 and P7 groups, normal saline subgroup for control study had intraperitoneal injection 0.9% normal saline 0.5mg/kg. Dexamethasone subgroup and acupuncture subgroup for experimental study had intraperitoneal injection 0.5mg/kg dexamethasone (Oradexon, Organon, Netherlands). P3 acupuncture subgroup neonatal rats had acupuncture Zusanli (ST-36) in P3,4,5 (post natal day 3,4,5) and were sacrificed in P6 (post natal day 6).
Zusanli (ST-36) is an acupoint located 3 mm lateral and distal to the anterior tubercle of the tibia of human. Zusanli (ST-36) was usefull in the treatment of cerebrovascular diseases in human and animals.
P7 acupuncture subgroup had acupuncture Zusanli (ST-36) in P7,8,9 (post natal day 7,8,9) and were sacrificed in P10 (post natal day 10).
Hippocampal dentate gyrus cells amounts and morphologic differences were observed through 5-bromo-2’-deoxyuridine (BrdU), Neuronal nuclei (NeuN, a neuronal marker) and Glial fibrillary acidic protein (GFAP, an astrocyte marker) immunohistochemistry methods. Nissl’s stain was used for counter staining. Immunofluorescence double labling method was used to identify the proliferating cells. Image Pro Plus (Media Cyberhetics, USA) was used for BrdU(+) cells density analysis. The hippocampal dentate gyrus anatomy is according to The Rat Brain compact third ediation, Paxions and Watson 1997.
The brain of neonatal rats brain development is equal to full term infants at P7. (Hagberg et al., 1997) Thus, P7 group was used to mimic full term infants under treatments.
The dexamethasone subgroup was using one single dose dexamethasone (0.5mg/kg) to mimic postnatal infant dosage. Intraperitoneal injection in P1 to mimic the preterm infants’ resuscitation status. Hippocampal dentate gyrus discontinuous with cells amount decreased was noted after dexamethasone injection in our previous study.
The results showed that dexamethasone lead to damage the hippocampus, and acupuncture Zusanli (ST-36) increased the dentate gyrus proliferation. Dexamethasone significantly decreased the increasing body weight/ P1 body weight then control group. In P3 normal saline and P7 acupuncture subgroups, the periventricular area also had BrdU(+) cells. Besides, the double labeling cells density of BrdU(+) & NeuN(+) were more than the density of BrdU(+) & GFAP(+) double labeling cells of the dentate gyrus .
In conclusion, acupuncture improve the dentate gyrus neuron damage caused by Dex. Acupuncture also increase the neuron cells proliferation in dentate gyrus.

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